bims-tuinly 2026-10-04 papers

bims-tuinly

Biomed News

on Tumor-infiltrating lymphocytes therapy

Issue of 2026–10–04
24 papers selected by
Pierpaolo Ginefra, Ludwig Institute for Cancer Research

Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes.
Immunometabolic Profiling of T Cells and Innate Lymphoid Cells Uncovers Therapeutic Targets to Enhance Immunotherapy in Head and Neck Cancer.
Dissociation between systemic inflammatory markers and the tumor microenvironment in predicting sentinel lymph node metastasis in cutaneous melanoma.
Association of tumor mutational burden and tumor-infiltrating lymphocytes with second primary cancer after complete resection of non-small cell lung cancer.
Correction: Stem-like CD4 T cells in tumors: an emerging framework for antitumor immunity.
High ZFP36 Family Expression in Exhausted T Cells Is Associated With Impaired Antitumor Effector Function.
IL-2/CD25 acts within the tumor microenvironment to reprogram tumor-specific cytotoxic CD8+ T cells while restraining regulatory T-cell accumulation.
Setanaxib Added to Pembrolizumab for Fibroblast-Rich, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: a Phase 2 Randomized Study.
SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer.
Coupling and uncoupling cell cycle and metabolism in CD8+ T cells.
HEATR1 deficiency enhanced gastric cancer cell PANoptosis to boost anti-tumor immunity.
Tumor-immune microenvironment and nutritional status biomarkers predict recurrence after total colectomy for locally advanced colon cancer: development and internal validation of a nomogram.
Thy1 retroviral reporters: a versatile platform for congenic background-independent adoptive transfer and CD8+ T cell differentiation studies.
Ras protein activator-like 3 is a key Ras GTPase-activating protein that protects the survival and anti-tumor activity of CD8+ T cells.
A Single-Cell-Derived CD8+ T-Cell State Plasticity Score for Prognostic Stratification and Characterization of Immune Responsiveness in Hepatocellular Carcinoma.
Navigating the immunosuppressive abyss: current hurdles and innovative breakthroughs in neoadjuvant immunotherapy for osteosarcoma.
Metabolic dysfunction and GZMK+ CD8+ T-cell remodeling in hepatocellular carcinoma: an evidence-stratified, hypothesis-generating review.
Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment.
Sex-associated miR-4286 is related to Breslow thickness and TILs in stage II/III primary cutaneous melanoma.
Potentiating immunotherapy in "immune-cold" solid tumors through orchestrating T cell immunity via tumor-specific genetic engineering.
Decidual-Like Natural Killer Cells Are Enriched in Melanomas and Acquire CD9 Through Melanoma Cell Contact.
In vivo CRISPR Screening Reveals LBR as a Regulator of CD8+ T Cell Fate Decision.
Magnetically Guided Macrophage Immunobots Coordinate Iron-Metabolic Cascades and Immunogenic Ferroptosis for Tumor Immunotherapy.
Reflections on adjuvant pembrolizumab for triple-negative breast cancer treated with the KEYNOTE-522 regimen: Is it really necessary?

Front Immunol. 2026 ;17 1957106

Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes.

Yi-Xiao Pan, Wei-Fei Chen, Rong Li, Meng-Jia Zhang, Zi-Yi Yan, Hui-Hui Xu.

   Background: Purpose of the study was to investigate the prognostic impact of HLA-G expression in patients with cervical squamous cell carcinoma (CSCC), and to further analyze its correlations with PD-L1 and CD8-positive (CD8+) tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME).
Methods: A total of 139 formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from patients diagnosed with CSCC. Immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) staining were performed to assess the expression of immune biomarkers, including HLA-G, its receptor ILT2, PD-L1, total TILs and CD8+ TILs.
Results: The overall positive expression rates were 86.8% for HLA-G, 85.1% for sHLA-G, 50.0% for PD-L1, and 70.2% for cases with low TIL infiltration in the TME. These immune biomarkers displayed distinct immunoreactivity patterns with remarkable intratumoral and stromal heterogeneity. ILT2 expression was positively correlated with CD8+ TIL infiltration in both intratumoral and stromal compartments, yet rare cellular co-localization between ILT2 and CD8 was detected. Within tumoral regions, a strong positive correlation was identified between HLA-G and PD-L1 expression, and the two proteins were confirmed to be co-localized at the single-cell level in SCC lesions. Using the median HLA-G expression level of 61.0% as the cutoff value, patients with HLA-G expression above this threshold showed significantly worse overall survival (OS). The subgroup with high HLA-G/sHLA-G and low TIL infiltration showed the worst prognosis.
Conclusions: The present study confirms that elevated HLA-G/sHLA-G expression serves as an independent adverse prognostic factor for cervical cancer. Combined assessment of HLA-G, PD-L1 and TIL infiltration may enable risk-stratified prognostic management for patients with cervical cancer.

Keywords:  CD8; HLA-G; ILT2; PD-L1; cervical squamous cell carcinoma; immune checkpoint (ICIs); tumor-infiltrating lymphocytes

DOI:  https://doi.org/10.3389/fimmu.2026.1957106
Cancer Immunol Res. 2026 Sep 28.

Immunometabolic Profiling of T Cells and Innate Lymphoid Cells Uncovers Therapeutic Targets to Enhance Immunotherapy in Head and Neck Cancer.

Sujeetha A Rajakumar, Namya Nanda, Chloe Kim, Dustin Dikeman, Tanguy Y Seiwert, Zubair Khan, Sewon Kang, Carole Fakhry, Martin P Alphonse.

Immunometabolic reprogramming governs antitumor immunity, yet its role in checkpoint blockade responses remains poorly defined. Using functional-metabolic flow cytometry, we characterized tumor-infiltrating mucosal-associated invariant T (MAIT) cells, CD8 T cells, and innate lymphoid cells (ILCs) from head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant anti-programmed cell death protein 1 (PD-1) monotherapy or combined anti-PD-1/anti-interleukin-8 (IL-8) therapy. We identified CD39-negative OX40 MAIT and CD8 tumor-infiltrating lymphocytes (TILs) as metabolically fit, less-exhausted populations. In contrast, OX40- cells exhibited elevated glucose-6-phosphate dehydrogenase (G6PD) expression, identifying the pentose phosphate pathway as a targetable metabolic vulnerability. Ex vivo transcriptomic analysis of CD8 TILs from untreated patients revealed CD39-stratified responses to anti-PD-1/polydatin (G6PD inhibitor) combination treatment: CD39-negative cells amplified effector programs; CD39-medium cells shifted toward lipid catabolism; and CD39-high exhausted cells showed downregulation of STAT3 and mTOR-pathway genes only under combination treatment, consistent with a shift in metabolic regulation. Secretome profiling confirmed the functional translation of this reprogramming, with combination treatment significantly increasing soluble CD27 secretion in CD39-high TILs-indicating enhanced activation in terminally exhausted populations. ILC profiling identified immunosuppressive CD294-high ILC2s, marked by elevated C-C-motif chemokine receptor 8 (CCR8) and carnitine palmitoyltransferase 1A (CPT1A) protein expression, as a potential barrier to checkpoint blockade efficacy. Conversely, CD39-negative ILC3s emerged as metabolically active populations amenable to therapeutic reprogramming. These findings establish immunometabolic profiling as a framework for guiding precision checkpoint blockade combinations in HNSCC.

DOI: https://doi.org/10.1158/2326-6066.CIR-26-0245
Melanoma Res. 2026 Sep 29.

Dissociation between systemic inflammatory markers and the tumor microenvironment in predicting sentinel lymph node metastasis in cutaneous melanoma.

Nilay Duman, Aslihan Özel, Damla Değirmenci, Banu Yaman, Ahmet Biçer, Yiğit Özer Tiftikcioglu, Işil Karaarslan, Ayşe Caner, Taner Akalin, Şaziye Burçak Karaca.

  Systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), are established prognostic biomarkers in melanoma, particularly in advanced disease. However, their utility in predicting early metastatic spread, such as sentinel lymph node (SLN) involvement, remains unclear. To evaluate the relative contributions of systemic inflammatory indices and tumor microenvironment (TME) features in predicting SLN metastasis in cutaneous melanoma. In this retrospective, single-center study, clinicopathological parameters, peripheral blood-derived inflammatory indices (NLR, PLR, lymphocyte-to-leukocyte ratio, lymphocyte-to-monocyte ratio, and neutrophil-to-eosinophil ratio), and TME features, including tumor-infiltrating lymphocytes (TILs) and tumor regression, were analyzed. Multivariable analyses and nested predictive models were constructed to identify independent predictors and to assess the incremental predictive value of each parameter group. SLN positivity was strongly associated with established histopathological markers, including Breslow thickness, ulceration, mitotic rate, and lymphovascular invasion (all P < 0.001). In contrast, systemic inflammatory indices showed no significant association with SLN involvement (all P > 0.05). TME-related features demonstrated significant associations; higher TIL density showed a dose-dependent inverse relationship with SLN positivity (P = 0.001), while tumor regression was linked to reduced nodal metastasis (P = 0.031). In addition, lower platelet counts were also associated with SLN positivity (P = 0.03). Incorporation of TME features improved model performance, whereas systemic inflammatory markers did not provide additional predictive value. Early nodal metastasis in melanoma appears to be driven by local tumor-immune interactions rather than systemic inflammation. These findings support the limited predictive value of circulating inflammatory markers and highlight the importance of TME features in risk stratification and clinical decision-making.

Keywords:  lymphocytes; melanoma; neoplasm metastasis; neutrophil–lymphocyte ratio; platelet–lymphocyte ratio; sentinel lymph node biopsy; tumor microenvironment; tumor-infiltrating

DOI:  https://doi.org/10.1097/CMR.0000000000001139
Front Oncol. 2026 ;16 1773288

Association of tumor mutational burden and tumor-infiltrating lymphocytes with second primary cancer after complete resection of non-small cell lung cancer.

Marie-Pier Gauthier, Maryam Karimi, Stefan Michiels, Lesley Seymour, Elisabeth Brambilla, Thierry Le-Chevalier, Jean-Charles Soria, Robert Kratzke, Stephen L Graziano, Ramaswamy Govindan, Ming-Sound Tsao, Frances A Shepherd.

   Introduction: The risk of developing second primary cancers (SPC) after complete surgical resection of non-small cell lung cancer (NSCLC) has been estimated at 1-2% per patient-year. We investigated whether tumor genomic instability, assessed by tumor mutational burden (TMB), and host immune response, assessed by tumor-infiltrating lymphocytes (TILs), were associated with the development of SPC.
Methods: Data from three randomized trials included in the Lung Adjuvant Cisplatin Evaluation-Biomarker (LACE-Bio) meta-analysis were used. TMB and TILs were assessed on FFPE specimens. TMB was categorized into tertiles (high >7.8 mutations/MB, moderate >4 to ≤7.8 mutations/MB, and low ≤4 mutations/MB), and TILs were classified as marked vs. other. Associations between biomarkers and competing endpoints (SPC, and death without developing SPC) were evaluated using Fine and Gray sub-distribution hazard models, stratified by trial and adjusted for treatment, age, sex, tumor stage, nodal stage, histology, performance status, and surgery type.
Results: TMB and TILs assessments were available for 879 patients with complete clinical covariates. Marked TILs was observed in 85 patients. During follow-up, 47 SPCs and 392 deaths without SPC were observed. No clear association was found between TMB or TILs and the cumulative incidence of SPC. In contrast, low TMB was associated with a higher cumulative incidence of death without SPC compared with moderate TMB (multivariable subdistribution hazard ratio (sHR) = 1.35 [95% confidence interval (CI), 1.06-1.72], p = 0.02). Marked TILs was associated with a lower cumulative incidence of death without SPC, although this association did not reach statistical significance after adjustment (multivariable sHR = 0.71 [95% CI, 0.46-1.10], p = 0.12).
Conclusion: This study is the first to evaluate associations between tumor genomic instability and host immune response, and competing endpoints of SPC and death without SPC in patients with completely resected NSCLC. No strong association was observed with SPC, whereas low TMB (compared with moderate TMB) was associated with the competing endpoint of death without developing SPC. Given the limited number of SPC events, these findings require confirmation in larger, independent cohorts of patients with early-stage lung cancer.

Keywords:  Lung Adjuvant Cisplatin Evaluation (LACE); biomarkers; non-small cell lung cancer (NSCLC); second primary cancer (SPC); tumor mutational burden (TMB); tumor-infiltrating lymphocytes (TILs)

DOI:  https://doi.org/10.3389/fonc.2026.1773288
Front Immunol. 2026 ;17 1984763

Correction: Stem-like CD4 T cells in tumors: an emerging framework for antitumor immunity.

Jiaxiang Xu, Yunchao Yang, Jun Zhang, Yue Zhang.

  [This corrects the article DOI: 10.3389/fimmu.2026.1853163.].

Keywords:  T cell differentiation; T cell stemness; TCF1; cancer immunotherapy; immune checkpoint blockade; stem-like CD4 T cells; tumor immunity; tumor microenvironment

DOI:  https://doi.org/10.3389/fimmu.2026.1984763
Cancer Sci. 2026 Sep 29.

High ZFP36 Family Expression in Exhausted T Cells Is Associated With Impaired Antitumor Effector Function.

Li Zhu, Youki Ueda, Yu Inutsuka, Toshifumi Ninomiya, Yuka Saeki, Takashi Inozume, Hiroko Watanabe, Takamasa Ishino, Hiroyoshi Y Tanaka, Kazuo Yamashita, Masakiyo Sakaguchi, Joji Nagasaki, Yosuke Togashi.

  Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reinvigorating antitumor immunity; however, a substantial proportion of patients show primary resistance or later relapse. To investigate T cell states associated with reduced ICI efficacy, we performed single-cell RNA sequencing (scRNA-seq) on tumor-infiltrating lymphocytes (TILs) from a patient experiencing rapid recurrence under PD-1 blockade. Our analysis identified elevated expression of the ZFP36 family of RNA-binding proteins within exhausted CD8+ T cells (Tex cells) in this progressing tumor. The ZFP36 family is known to destabilize target mRNAs by binding to AU-rich elements in their 3' untranslated regions (3' UTRs). In EL4 T cells, Zfp36 overexpression accelerated the decay of the effector cytokine mRNAs Tnf, Il2, and Ifng, thereby impairing cytokine production. This process is exacerbated by hypoxia. Furthermore, high ZFP36 family expression correlates with poor prognosis in ICI-treated patients in a public bulk tumor transcriptomic dataset. These findings suggest that tumor microenvironment (TME)-induced hypoxia upregulates the ZFP36 family in Tex cells, which in turn suppresses cytokine production via post-transcriptional regulation, potentially contributing to impaired antitumor effector function.

Keywords:  PD‐1 blockade; T cell exhaustion; ZFP36 family; hypoxia; post‐transcriptional regulation

DOI:  https://doi.org/10.1111/cas.70546
J Immunother Cancer. 2026 Sep 29. pii: e015104. [Epub ahead of print]14(9):

IL-2/CD25 acts within the tumor microenvironment to reprogram tumor-specific cytotoxic CD8+ T cells while restraining regulatory T-cell accumulation.

Kathryn M LaPorte, Janika Põder, Daria Ivanova, Molly Dalzell, Paolo Serafini, Alejandro V Villarino, Thomas R Malek.

   BACKGROUND: Targeting the high-affinity interleukin-2 receptor (IL-2R) on CD8+ T effector cells elicits potent antitumor responses that are augmented when co-administered with programmed cell death protein 1 (PD-1) blockade.
METHODS: Using the mouse IL-2/CD25 fusion protein (mIL-2/CD25) at a high dose (HD) and anti-PD-1 checkpoint blockade, with the CT26 and MC38 colon carcinomas as models, the current study investigated how antitumor responses occurred when regulatory T cells (Tregs) are also a target of HD mIL-2/CD25. Single-cell RNA sequencing (scRNA-seq) and T-cell receptor (TCR) repertoire analysis of tumor-associated immune cells were used to identify how combination therapy reshaped the tumor microenvironment (TME). These data were cross-referenced with published datasets to (1) corroborate TCR specificity and (2) identify how CD8+ T-cell differentiation is affected by different IL-2/PD-1 strategies.
RESULTS: Here, we show that effective antitumor immunity by the combination therapy is a result of HD mIL-2/CD25-dependent reprogramming of CD8+ tumor-specific T cells that increases their function and supports their expansion within the TME, the latter also shaped by PD-1 blockade. This therapy supports antitumor responses by chemokines and inflammatory cytokines that selectively favor the migration of CD8+ T cells but not Tregs deep within the tumor. After HD mIL-2/CD25 treatment, Tregs within the TME showed impaired downstream IL-2R signaling, reflected by failed upregulation of forkhead box P3 and CD25, impaired development into effector Tregs, and enhanced cell death, the latter which likely offsets Treg proliferation. Many similarities were noted after direct comparison of these scRNA-seq findings with another study where IL-2 activity was targeted to PD-1+ CD8+ T cells. Notably, HD mIL-2/CD25 and anti-PD-1 combination promotes effector and 'stem-like' CD8+ T-cell subsets, perhaps even to a greater extent than the PD-1-targeted IL-2 strategy.
CONCLUSIONS: The efficient differentiation of exhausted CD8+ T cells into highly functional cells and the resulting potent antitumor responses by HD mIL-2/CD25 plus anti-PD-1 suggest that this approach may augment durable response rates more than currently achieved with checkpoint blockade monotherapy.

Keywords:  Immune Checkpoint Inhibitor; Immunotherapy; T cell; T regulatory cell - Treg; Tumor microenvironment - TME

DOI:  https://doi.org/10.1136/jitc-2026-015104
Cancer Res Commun. 2026 Oct 01.

Setanaxib Added to Pembrolizumab for Fibroblast-Rich, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: a Phase 2 Randomized Study.

Jérôme Fayette, Gareth J Thomas, Amaury Daste, Maciej Rotarski, Beatriz Castelo, Antonio Rullan, Aaron Levine, Richard Philipson, Benjamin H Jenkins, Kevin J Harrington.

Purpose Efficacy of checkpoint inhibitors (e.g., pembrolizumab) in head and neck squamous cell carcinoma (HNSCC) is limited by cancer-associated fibroblasts (CAFs). This randomized, double-blind, placebo-controlled, phase 2 trial (NCT05323656) evaluated the efficacy and safety of the reactive oxygen species inhibitor setanaxib with pembrolizumab in patients with CAF-rich HNSCC. Patients and Methods Participants (≥18 years) with recurrent or metastatic HNSCC with CAF tumor levels ≥5% received setanaxib (800 mg orally bid) or placebo for ≤105 weeks, plus intravenous pembrolizumab (200 mg q3w). The primary outcome was best percentage change from baseline in tumor size. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and changes in tumor levels of CAFs, CD8+ tumor-infiltrating lymphocytes (TILs), and FOXP3+ T-regulatory cells at week 9. Results Fifty-five participants (setanaxib, n = 27; placebo, n = 28) were treated. Least squares (LS) mean (SE) best percentage changes in tumor size from baseline values were -7.9% (9.3%) (setanaxib) and -12.9% (9.0%) (placebo) (LS mean difference [80% CI]: 5.1 [-11.9, 22.0]; P = 0.7008). PFS hazard ratio (HR) (80% CI) was 0.58 (0.38, 0.89), favoring setanaxib (P = 0.1023 [threshold <0.2]). OS HR (80% CI) was 0.45 (0.24, 0.85), also favoring setanaxib (P = 0.1057). Transcriptomic analyses identified a significant increase in CD8+ TILs with setanaxib (P = 0.037) but not placebo. There were 33 serious adverse events (16 setanaxib, 17 placebo), leading to four deaths (all placebo). Conclusions These improvements in PFS, OS, and CD8+ TILs can guide further setanaxib research in patients with solid tumors.

DOI: https://doi.org/10.1158/2767-9764.CRC-26-0422
Adv Sci (Weinh). 2026 Sep 27. e77909

SPRED2 Negatively Regulates CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer.

Miao Tian, Teizo Yoshimura, Kun Zhao, Chunning Li, Tong Gao, Ziyi Wang, Masayoshi Fujisawa, Toshiaki Ohara, Akihiro Matsukawa.

  Activation of the RAS/RAF/ERK pathway is crucial for adaptive immunity. Here, we provide evidence that Sprouty-related EVH1 domain containing 2 (SPRED2), an endogenous inhibitor of this pathway, negatively regulates CD8+ T cell-mediated antitumor immunity in breast cancer. In EO771 and 4T1 mouse models, Spred2-/- mice exhibit reduced tumor growth, with lower endpoint lung metastatic burden in the 4T1 model, accompanied by increased T-cell infiltration and activation. Spred2-/- T cells show enhanced cytokine expression, proliferation, survival, in vitro cytotoxicity, and memory-like phenotypes, particularly among CD8+ T cells. Adoptive transfer of Spred2-/- CD8+ T cells into tumor-bearing wild-type hosts similarly reduces endpoint lung metastatic burden. MEK inhibition with U0126 attenuates increased interferon-gamma and granzyme B expression in Spred2-/- CD8+ T cells. Transcriptomic analyses reveal an inverse correlation between SPRED2 expression and antitumor CD8+ T cell states in both humans and mice. In tumor-infiltrating T cells from patients with breast cancer, SPRED2low T cells show enriched effector and cytotoxicity programs and are associated with "immune-hot" tumors, whereas survival associations vary with CD8+ T cell context. Collectively, these findings suggest that SPRED2 functions as a cell-intrinsic negative regulator of CD8+ T-cell activation and highlight its potential as a therapeutic target to enhance T cell-based cancer immunotherapy.

Keywords:  CD8+ T cells; MAPK/ERK; breast cancer; immunotherapy; tumor microenvironment

DOI:  https://doi.org/10.1002/advs.77909
Trends Immunol. 2026 Sep 29. pii: S1471-4906(26)00256-5. [Epub ahead of print]

Coupling and uncoupling cell cycle and metabolism in CD8+ T cells.

Floortje J van Haften, Hanna S Hepp, Melissa Biemond, Ramon Arens.

  CD8+ T cells eliminate infected and malignant cells through coordinated proliferation and effector differentiation, processes supported by metabolic reprogramming that together form an interconnected, cross-regulated network. Emerging evidence indicates, however, that cell cycle progression and effector programming can be transiently uncoupled, with implications for T cell function and fate. Short-term modulation of cell cycle dynamics creates a window for metabolic rewiring, reshaping nutrient utilization, cytokine responsiveness, and bioenergetic capacity. This uncoupling can enhance T cell expansion, effector function, and antitumor activity. Collectively, these findings indicate that the cell cycle functions as an instructive checkpoint integrating metabolic and differentiation programs, not merely supporting proliferation. Understanding this interplay provides a conceptual framework to optimize T cell-based immunotherapies and rationally design chemoimmunotherapy combinations.

Keywords:  CD8(+) T cells; T cell differentiation; adoptive cell transfer; cell cycle progression; immunotherapy; metabolic reprogramming

DOI:  https://doi.org/10.1016/j.it.2026.09.001
Mol Med. 2026 Sep 04. pii: 166. [Epub ahead of print]32(1):

HEATR1 deficiency enhanced gastric cancer cell PANoptosis to boost anti-tumor immunity.

Ya Huang, Qingcheng Xu, Meijuan Zhu, Yawei Shen, Xianwen Zhang.

   BACKGROUND: Despite the promise of immune checkpoint inhibitors (ICIs) for gastric cancer (GC) treatment, limited cytotoxic T cell infiltration remains a major barrier to therapeutic efficacy. This study investigates whether targeting HEAT repeat containing 1 (HEATR1) can induce immunogenic PANoptosis to enhance anti-tumor immunity.
METHODS: Bioinformatics analysis of TCGA-STAD cohort, syngeneic mouse models, and patient-derived organoids (PDOs) were employed to assess HEATR1 function. Mechanistic studies examined STAT1/IRF1 signaling, PANoptosis markers, and dendritic cell (DC) activation. Therapeutic efficacy was evaluated in combination with anti-PD1 immunotherapy.
RESULTS: HEATR1 expression inversely correlated with CD8+ T cell infiltration in GC tissues and was associated with advanced tumor stage and lymph node metastasis. HEATR1 knockdown suppressed tumor growth in immunocompetent but not T cell-deficient mice, demonstrating immune-dependency. Mechanistically, HEATR1 deficiency stabilized STAT1 by inhibiting proteasome-mediated degradation, thereby sensitizing GC cells to IFN-γ-induced PANoptosis through STAT1/IRF1 signaling activation. This inflammatory cell death released damage-associated molecular patterns, which promoted DC maturation and cross-priming of CD8+ T cells. The resulting IFN-γ secretion established a positive feedback loop amplifying tumor cell PANoptosis. PDO models confirmed that HEATR1-silenced organoids exhibited enhanced PANoptosis and DC-mediated CD8+ T cell expansion. HEATR1 knockdown synergized with anti-PD1 therapy to significantly inhibit tumor progression.
CONCLUSIONS: HEATR1 deficiency enhances GC cell sensitivity to IFN-γ-mediated PANoptosis via STAT1/IRF1 pathway activation, creating an immunogenic tumor microenvironment that potentiates ICI efficacy. These findings identify HEATR1 as a promising therapeutic target for improving GC immunotherapy outcomes.

Keywords:  CD8+ T cells; Dendritic cells; Gastric cancer; Immunogenic cell death; PANoptosis; Patient-derived organoids

DOI:  https://doi.org/10.1186/s10020-026-01574-6
Front Genet. 2026 ;17 1916575

Tumor-immune microenvironment and nutritional status biomarkers predict recurrence after total colectomy for locally advanced colon cancer: development and internal validation of a nomogram.

Yanhui Yang, Meng Gao, Songchun Liu, Qiong Yang.

   Background: Post-colectomy recurrence affects 25%-45% of patients with locally advanced colon cancer despite adjuvant chemotherapy. The tumor-immune microenvironment (TIME)-encompassing mismatch repair (MMR) status, tumor-infiltrating lymphocyte (TIL) density, PD-L1 expression, and systemic indices such as the neutrophil-to-lymphocyte ratio (NLR)-critically determines recurrence risk and immunotherapy response. Perioperative nutritional status (preoperative albumin; NRS 2002) further modulates immune competence. No validated clinical tool has integrated these multi-dimensional biomarkers for post-colectomy risk stratification.
Methods: This retrospective dual-centre cohort enrolled 341 patients (stage II-III colon cancer; total colectomy, 2020-2024). Tumour-immune biomarkers (MMR/MSI status, PD-L1 CPS, TIL density, NLR, PLR) and nutritional indicators (albumin, NRS 2002) were assessed preoperatively. Primary endpoint: 3-year disease-free survival (DFS). A nomogram was constructed from multivariable Cox regression and internally validated by 1,000-resample bootstrapping; performance was assessed by AUC, calibration, and decision curve analysis.
Results: Among 341 patients (median follow-up 36.0 months), 94 (27.6%) recurred; 3-year DFS was 72.4%. Independent predictors of inferior DFS: pMMR/MSS status (aHR = 2.84), advanced stage (aHR = 2.52), high lymph node ratio (aHR = 2.13), low TIL density (aHR = 2.21), elevated CEA (aHR = 1.88), and high NLR (aHR = 1.78; all p ≤ 0.008). Preoperative albumin (aHR = 0.94 per 1 g/L increase, p = 0.003) and NRS 2002 >=4 (aHR = 1.58, p = 0.035) also remained independently associated with DFS. Adjuvant ICI use was associated with improved DFS (aHR = 0.48, p = 0.005). The nomogram achieved AUC = 0.841 (optimism-corrected: 0.824), good calibration (Hosmer-Lemeshow p = 0.557), and net clinical benefit across threshold probabilities 0.10-0.80.
Conclusion: A nomogram integrating MMR status, TIL density, PD-L1 CPS, NLR, CEA, tumour stage, lymph node ratio, and perioperative nutritional indicators robustly predicts 3-year recurrence after total colectomy for locally advanced colon cancer (AUC = 0.841), substantially outperforming clinical-only models. These hypothesis-generating findings require prospective randomised validation before clinical implementation.

Keywords:  NLR; albumin; biomarker; colon cancer; disease-free survival; immune checkpoint inhibitor; mismatch repair; nomogram

DOI:  https://doi.org/10.3389/fgene.2026.1916575
Front Immunol. 2026 ;17 1917932

Thy1 retroviral reporters: a versatile platform for congenic background-independent adoptive transfer and CD8+ T cell differentiation studies.

Chunlong Liu, Chunling Liu, Jing Zhong, Xiaodi Yang, Dapeng Wang.

  Adoptive T cell transfer remains a fundamental technique for dissecting the molecular mechanisms governing T cell differentiation. A successful adoptive-transfer experiment typically relies on labor-intensive construction of specific congenic mouse strains to distinguish donor from host cells. This limitation may be addressed by a readily detectable surface reporter. Thy1 is a candidate, but it remains unclear whether it is a reliable reporter for monitoring adoptively transferred CD8+ T cell differentiation because Thy1 is a functional protein involved in thymic development and cell activation. To address this question, we systematically evaluated the reliability, stability, and functional neutrality of Thy1.1 and Thy1.2, two Thy1 isoforms, as adoptive-transfer reporters during CD8+ T cell differentiation in vivo. Our results show that endogenous Thy1 expression remains stable across the differentiation stages examined. In the experimental settings tested, exogenous Thy1 reporter expression did not measurably alter the assessed differentiation phenotypes or donor-cell recovery. We further constructed and validated a Thy1 reporter-based platform that captured phenotypes associated with both loss-of-function (shRNA) and gain-of-function (cDNA) modulation of the transcription factor T-bet. This system provides a practical option for congenic background-independent adoptive transfer and genetic studies of CD8+ T cell differentiation.

Keywords:  CD8+ T cell differentiation; T-bet; adoptive transfer; retroviral vector; thy1

DOI:  https://doi.org/10.3389/fimmu.2026.1917932
Front Immunol. 2026 ;17 1893111

Ras protein activator-like 3 is a key Ras GTPase-activating protein that protects the survival and anti-tumor activity of CD8+ T cells.

Zhenzi Peng, Xinyi Zhou, Alato Okuno, Derick Okwan-Duodu, Suguru Saito.

  Ras signaling plays an essential role in immune cell function; however, its activity must be precisely controlled to prevent excessive activation and associated cellular dysfunction. In this study, we identify the leukocyte-specific Ras GTPase-activating protein (RasGAP) RASAL3 as an important regulator of CD8+ T cell homeostasis and anti-tumor immunity. Following T cell receptor (TCR) stimulation, RASAL3-deficient CD8+ T cells display sustained Ras activation, resulting in increased activation-induced cell death (AICD). The surviving RASAL3-deficient CD8+ T cells exhibit impaired effector functions, including reduced cytokine production and decreased tumor-killing activity. Using an in vivo B16-F10 melanoma model, we found that CD8+ T cell-specific RASAL3-deficient mice (R3fl/flCd8-Cre) develop significantly faster tumor growth compared with control mice. Although Programmed death protein 1 (PD-1) blockade partially restores anti-tumor responses in these mice, the therapeutic effect remains markedly weaker than that observed in control animals. In human melanoma samples, RASAL3 expression is reduced in tumor-infiltrating CD8+ T cells. Furthermore, patients with metastatic melanoma show lower RASAL3 expression in primary tumors compared with patients without metastasis, and higher RASAL3 expression in CD8+ T cells within primary lesions is associated with improved overall survival. Together, these findings reveal that RASAL3 is required for the maintenance of CD8+ T cell survival and effector activity. Reduced RASAL3 expression may represent a mechanism by which tumors evade immune surveillance, and RASAL3 expression in CD8+ T cells may serve as a potential biomarker for predicting clinical outcomes in melanoma.

Keywords:  CD8+ T cells; RASAL3; RasGAP; anti-tumor immunity; melanoma

DOI:  https://doi.org/10.3389/fimmu.2026.1893111
Immunotargets Ther. 2026 ;15 626002

A Single-Cell-Derived CD8+ T-Cell State Plasticity Score for Prognostic Stratification and Characterization of Immune Responsiveness in Hepatocellular Carcinoma.

Le Xing, Dan He, Dong-Mei Li, Zhong Liang, Chen Yue, Cheng-Yang Zhang, Ying-Chen Hou, Chen-Yu Jiang, Guang-Ding Zhou, Hongjiao Yu, Yan-Ling Zhang, Yan-Xia Shi, Lin-Hai Li, Ming Liu.

   Background: T cells play a central role in antitumor immunity. Emerging evidence indicates that T-cell plasticity and differentiation states are associated with clinical outcomes and responses to cancer immunotherapy. CD8⁺ T cells that retain differentiation potential are thought to sustain effective antitumor immunity. However, robust quantitative metrics for assessing tumor-infiltrating CD8+ T-cell state plasticity and defining its clinical significance in hepatocellular carcinoma remain lacking.
Methods: We integrated publicly available single-cell RNA-sequencing datasets from HCC cohorts to characterize CD8⁺ T-cell states using unsupervised pseudotime reconstruction and supervised ordinal transcriptional modeling. We used genes showing progressive changes along the inferred state axis and enriched in CD8⁺ T cells to develop a T-cell State Plasticity score using Cox proportional hazards and LASSO regression in the training cohort. The model was evaluated in independent bulk transcriptomic cohorts.
Results: Supervised psupertime analysis validated the predefined Tcm-Tem-Tpex-Ttex ordinal axis in held-out cells, supporting the existence of an ordered CD8⁺ T-cell state continuum in HCC. The CD8+ T-cell State Plasticity score robustly stratified clinical outcomes across multiple large HCC cohorts. High-risk scores, indicative of reduced CD8+ T-cell state plasticity, were associated with adverse clinical outcomes and an immunosuppressive tumor immune microenvironment.
Conclusion: CD8+ T-cell states are associated with tumor immune characteristics and clinical outcomes in HCC. This single-cell-derived T cell plasticity scoring system provides a quantitative framework for prognostic prediction and immune landscape evaluation, with potential implications for clinical decision-making.

Keywords:  hepatocellular carcinoma; prognostic stratification; risk scoring model; tumor immune microenvironment

DOI:  https://doi.org/10.2147/ITT.S626002
Front Immunol. 2026 ;17 1837053

Navigating the immunosuppressive abyss: current hurdles and innovative breakthroughs in neoadjuvant immunotherapy for osteosarcoma.

Guanghao Chen, Minjie Hu, Zhongkun Li, Kunpeng Yang, Bao Chen, Tianhao Xu.

  Osteosarcoma is the most common primary malignant bone tumor of children and adolescents. Multiagent neoadjuvant chemotherapy once improved survival substantially, but outcomes have since plateaued. Delivering immunotherapy before surgery is attractive because the primary tumor, the tumor immune microenvironment (TIME), and the tumor-draining lymph nodes (TDLNs) remain intact. This setting may allow the TIME to be reconfigured while antigen sampling and T-cell priming are still possible. It does not, however, make the tumor a vaccine, nor does it imply that expanded tumor-infiltrating lymphocytes are tumor specific. Any benefit is instead likely to depend on antigen quality, human leukocyte antigen (HLA)-mediated presentation, the availability of tumor-reactive T-cell clones, and the reversibility of local immunosuppression. Translation remains constrained by a low but heterogeneous mutational burden, a myeloid-dominated microenvironment, and the absence of validated selection biomarkers. Preoperative treatment must also preserve its established non-immunological goals, namely downstaging to enable limb salvage and control of micrometastatic disease. We therefore examine the biological rationale, the current evidence, and the surgical, radiological, and pathological barriers to translation. We additionally consider how structural genomic instability constrains antigen availability and presentation, and how natural killer cell-directed strategies may inform barrier-matched design. On this basis we propose a barrier-matched development framework in which pathological response, spatial multi-omics, and molecular clearance jointly define success.

Keywords:  genomic instability; natural killer cells; neoadjuvant immunotherapy; osteosarcoma; pathological response assessment; tumor immune microenvironment; tumor-draining lymph nodes

DOI:  https://doi.org/10.3389/fimmu.2026.1837053
Front Immunol. 2026 ;17 1963310

Metabolic dysfunction and GZMK+ CD8+ T-cell remodeling in hepatocellular carcinoma: an evidence-stratified, hypothesis-generating review.

Qianqian Zhong, Wanruo Lyu, Jieying Li, Yiming Song, Yunxin Huang, Chunbin Wang, Juling Ji.

  Type 2 diabetes mellitus and metabolic dysfunction associated steatotic liver disease contribute to the growing burden of hepatocellular carcinoma, yet their effects on hepatic antitumor immunity remain incompletely defined. Recent single-cell and spatial profiling studies indicate that hepatocellular carcinoma contains diverse CD8+ T cell states, including cytotoxic, exhausted, tissue-resident, progenitor-like, and transitional phenotypes. This review synthesizes evidence linking hyperglycemia, insulin resistance, lipotoxic injury, chronic inflammation, fibrosis, altered antigen presentation, stromal remodeling, chemokine signaling, and nutrient availability to CD8+ T-cell remodeling in HCC arising in the context of metabolic dysfunction. Particular attention is given to GZMK+ CD8+ T cells, which may reflect non-terminal differentiation, inflammatory adaptation, or transitional immune states rather than conventional cytotoxic effector function. Although GZMK-high CD8+ T cell populations have been reported in hepatocellular carcinoma and therapy-associated immune contexts, direct evidence that type 2 diabetes induces these cells in the liver remains limited. This review specifically examines GZMK+ CD8+ T-cell states within the immunometabolic context of HCC, distinguishes direct hepatic and tumor evidence from extrapolated findings in metabolic liver disease and other inflammatory conditions, and proposes a testable framework for phenotypic, spatial, and functional validation. Integrated single-cell, spatial, protein level, T cell receptor clonality, functional, and clinical studies are needed to define their biological significance and translational value.

Keywords:  CD8+ T cells; GZMK; hepatocellular carcinoma; immunometabolism; tumor microenvironment

DOI:  https://doi.org/10.3389/fimmu.2026.1963310
Adv Sci (Weinh). 2026 Sep 30. e77518

Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment.

Chao Liang, Jiaqi He, Wan-Ru Zhuang, Yao Lei, Yanru Jiang, Xianbin Ma, Pan Liu, Zhujun Jiang, Yongheng Li, Hai-Yan Xie.

  Despite considerable advances in cancer immunotherapy, the persistent immunosuppressive tumor microenvironment (TME) seriously limits its performance in solid tumors. Here, we reveal that trogocytosis-an intercellular membrane transfer process-between tumor-associated macrophages (TAMs) and cancer cells serves as a critical mechanism driving this immunosuppression. We demonstrate that trogocytosis efficiency, inversely correlated with tumor cell cortical stiffness, varies substantially across cancer types and dictates immunosuppressive intensity through upregulation of CXCL5 and Arg-1, leading to CD8+ T cell exhaustion. Importantly, this mechano-immunological axis is conserved in humans, as evidenced by study with human cell lines and a strong correlation between trogocytosis markers and T cell exhaustion in clinical patient samples. Increasing tumor cell stiffness with simvastatin effectively suppressed trogocytosis, reversed T cell dysfunction, and synergistically enhanced the efficacy of adoptive T cell therapy. These findings establish macrophage trogocytosis as a fundamental driver of immunosuppressive heterogeneity and highlight its targeting as a promising strategy to potentiate cancer immunotherapy.

Keywords:  T cell exhaustion; cortical stiffness; immunosuppressive heterogeneity; trogocytosis; tumor‐associated macrophages

DOI:  https://doi.org/10.1002/advs.77518
medRxiv. 2026 Sep 10. pii: 2026.09.04.26362289. [Epub ahead of print]

Sex-associated miR-4286 is related to Breslow thickness and TILs in stage II/III primary cutaneous melanoma.

InterMEL Consortium

Sex differences in melanoma incidence and mortality are well-established. Previous work has shown that the female survival advantage can be largely explained by differences in clinico-pathologic features, such as age, Breslow thickness, ulceration, mitoses, and primary site. Here we test the hypothesis that sex-differentiated expression of micro-RNAs (miRNAs) may be associated with sex differences in melanoma pathology. In a sample of 715 AJCC stage II/III primary melanomas from the InterMEL project, we find two miRNAs (miR-361 and miR-4286) that are differentially expressed in males and females, and further find one of these (miR-4286) to be associated with both greater Breslow thickness and the presence of brisk tumor infiltrating lymphocytes (TILs). These results suggest that miR-4286 may be a candidate marker for sex differences in melanoma pathology. Functional experiments may confirm whether this relationship is causal or purely associative.

DOI: https://doi.org/10.64898/2026.09.04.26362289
Cell Rep Med. 2026 Sep 26. pii: S2666-3791(26)00527-6. [Epub ahead of print] 103110

Potentiating immunotherapy in "immune-cold" solid tumors through orchestrating T cell immunity via tumor-specific genetic engineering.

Jiaqi He, Chunguang Zhang, Chao Liang, Wenchi Xue, Yongheng Li, Lili Dai, Chunyuan Liu, Wan-Ru Zhuang, Xianbin Ma, Ran Cheng, Yao Lei, Weidong Nie, Hai-Yan Xie.

DOI: https://doi.org/10.1016/j.xcrm.2026.103110
medRxiv. 2026 Sep 21. pii: 2026.09.18.26363442. [Epub ahead of print]

Decidual-Like Natural Killer Cells Are Enriched in Melanomas and Acquire CD9 Through Melanoma Cell Contact.

Natalie A Vandeven, Christopher E Collora, Claire Muckle, Sofia Celli, Jessica S W Borges, Kylie Michel, Victoria Sorensen, Katherine Foley, Katherine M Kichula, Martin D McCarter, Sapna P Patel, Kasey L Couts, William A Robinson, Richard P Tobin, Paul J Norman.

Natural killer (NK) cells at the maternal-fetal interface harbor a specialized decidual phenotype that promotes placentation and immune tolerance. Although it has been postulated that tumors can exploit similar NK cell programs to augment the tumor microenvironment, this mechanism has not been investigated in melanoma. Using flow cytometry and multiplex immunohistochemistry, we identified CD56 Bright CD16 - CD49a + CD9 + decidual-like NK (dl-NK) cells within melanoma tumors; these cells were rare or absent in peripheral blood from either patients with melanoma or healthy donors. These dl-NK cells were detected within and surrounding melanoma tumors in both male and female patients and across melanoma subtypes and across primary, lymph node, and distant metastatic sites. In an exploratory cohort of patients treated with tumor-infiltrating lymphocyte therapy, higher dl-NK frequency was observed in the patient with progressive disease. Because CD9 is a defining feature of decidual NK cells, we examined the relationship of CD9 with the dl-NK phenotype. Tumor CD9 expression was positively associated with intratumoral dl-NK frequency (Pearson rho = 0.40, p = 0.056). Direct co-culture of healthy donor NK cells with CD9-expressing melanoma cells induced robust CD9 acquisition by CD56 Bright NK cells, whereas separation by a transwell abrogated this effect, demonstrating a requirement for direct cell-cell interaction. Collectively, these findings identify a dl-NK cell population within melanomas and suggest that direct interactions with melanoma cells may contribute to acquisition of this phenotype, revealing a potential immunologic parallel between the melanoma microenvironment and the maternal-fetal interface.

DOI: https://doi.org/10.64898/2026.09.18.26363442
FASEB J. 2026 Oct 15. 40(19): e72318

In vivo CRISPR Screening Reveals LBR as a Regulator of CD8+ T Cell Fate Decision.

Qiying Zhang, Shuya Chang, Shengli Zhao, Weixin Zhang, Rong Wang, Mingyang Zhong, Guanfeng Liu, Xiaojing Li, Ao Guo.

  CD8+ T cells play an important role in anti-infection and anti-tumor immunity. Metabolic reprogramming has emerged as a critical regulator of T cell function, yet the roles of specific cholesterol-associated proteins during T cell fate trajectories remain unclear. Here, using an in vivo CRISPR screen in CD8+ T cells during infection with a customized sgRNA library targeting key cholesterol metabolism-associated proteins, we successfully identified several candidate targets, including the LBR (Lamin B Receptor). Lbr knockout significantly reduced the proportion and absolute number of short-lived effector cells (SLECs), severely impairing effector responses, while concomitantly increasing the memory precursor population upon LCMV infection. Furthermore, transcriptomic analysis revealed that Lbr depletion markedly altered signaling pathways governing effector T cell differentiation. These findings reveal the role of LBR in modulating effector and memory T cell differentiation, suggesting it as a potential target for metabolic reprogramming to enhance T cell-based immunotherapies.

Keywords:  CD8+ T cells; LBR; T cell fate decisions; cholesterol metabolism; in vivo CRISPR screen

DOI:  https://doi.org/10.1096/fj.202602909R
Adv Sci (Weinh). 2026 Sep 27. e77760

Magnetically Guided Macrophage Immunobots Coordinate Iron-Metabolic Cascades and Immunogenic Ferroptosis for Tumor Immunotherapy.

Xirui Zeng, Yingfei Zhang, Chong Wu, Qijia Duan, Mengqi Fan, Kuan Wang, Shirong Cai, Immihan Ceren Yasa.

  Adoptive cell therapy (ACT) remains challenging in solid tumors, where poor tumor infiltration, metabolic heterogeneity, and an immunosuppressive tumor microenvironment (TME) constrain therapeutic efficacy. Here, we developed magnetically and metabolically programmed macrophage-based immune microrobots (immunobots) for active solid tumor immunotherapy. The immunobots are constructed by loading bone marrow-derived macrophages (BMDMs) with lipopolysaccharide (LPS)-modified Janus L10-FePt magnetic microrollers (LMRs), which function both as an external magnetic actuation unit and as biochemical regulators that program macrophages into an anti-tumor phenotype. Optimized LMR loading endows the immunobots with robust propulsion, retention under flow, and enhanced barrier penetration. LMRs drive M1-like polarization through LPS-induced inflammatory activation and FePt-derived labile iron-amplified oxidative stress, leading to altered iron homeostasis, elevated reactive oxygen species (ROS), and enhanced NF-κB signaling. Functionally, immunobots induce ferroptosis-associated immunogenic cell death (ICD) in tumor cells. In vivo, magnetically guided immunobots suppress tumor growth through coordinated remodeling of the tumor immune landscape, including tumor-associated macrophage (TAM) reprogramming, dendritic cell maturation, and enhanced CD8+ T cell activation. Collectively, this work establishes a magnetically guided and metabolically programmed microrobotic immunotherapy strategy for overcoming the physical, metabolic, and immunological barriers that limit cellular therapy in solid tumors.

Keywords:  biohybrid microrobots; cellular immunotherapy; ferroptosis; magnetic actuation; targeted tumor therapy

DOI:  https://doi.org/10.1002/advs.77760
Eur J Cancer. 2026 Sep 24. pii: S0959-8049(26)00846-4. [Epub ahead of print]248 117064

Reflections on adjuvant pembrolizumab for triple-negative breast cancer treated with the KEYNOTE-522 regimen: Is it really necessary?

Vitor T Liutti, Hans Wildiers, Gabe S Sonke, Patrick Neven.

  Gains in event-free and overall survival from the KEYNOTE-522 trial have incorporated pembrolizumab into the neoadjuvant and adjuvant armamentarium for stage II-III triple-negative breast cancer (TNBC). However, the lack of a second randomization to pembrolizumab after surgery raises the question of whether the adjuvant phase of this immunotherapeutic agent is necessary, both in patients who achieve a pathological complete response (pCR) and in those with residual disease. Thus, the KEYNOTE-522 design established the use of adjuvant pembrolizumab as current standard of care without demonstrated benefit of the adjuvant part. Some studies in patients with specific types of cancer, including TNBC, suggest that adjuvant immunotherapy may not provide a benefit. Furthermore, no study has evaluated the role of adjuvant immunotherapy specifically following neoadjuvant chemoimmunotherapy. Additionally, concerns regarding chronic toxicities and the use of health care resources including costs of the adjuvant treatment have raised concerns in the oncologic community. Baseline presence of tumor-infiltrating lymphocytes and absence of circulating tumor DNA or specific molecular subtypes are associated with pCR and have been proposed as biomarkers predicting outcomes in trials of immunotherapy in localized TNBC, but no data on these biomarkers from the KEYNOTE-522 trial have been published to clarify the benefit of adjuvant pembrolizumab. This commentary discusses the available evidence, ongoing controversies, knowledge gaps and future perspectives regarding adjuvant immunotherapy in early TNBC.

Keywords:  Adjuvant therapy; Breast cancer; Pembrolizumab; Triple-negative

DOI:  https://doi.org/10.1016/j.ejca.2026.117064