bims-tuinly Biomed News
on Tumor-infiltrating lymphocytes therapy
Issue of 2025–01–12
six papers selected by
Pierpaolo Ginefra, Ludwig Institute for Cancer Research
  1. Association of stromal tumor-infiltrating lymphocytes with clinicopathological parameters in endometrial cancer.
  2. White Depressed Areas and Tumor Infiltrating Lymphocytes: The Cancer Cure That Lies Within?
  3. Adoptive cell therapies in thoracic malignancies: a comprehensive review.
  4. Prognostic value of tumor-infiltrating lymphocyte subtypes and microorganisms in triple-negative breast cancer.
  5. Human γδ T cells in the tumor microenvironment: Key insights for advancing cancer immunotherapy.
  6. CD3+ Tumor-Infiltrating Lymphocytes in Breast Carcinoma: Their Prognostic Role and Association With Clinical Parameters.
  1. Korean J Clin Oncol. 2024 Dec;20(2): 74-78
    Association of stromal tumor-infiltrating lymphocytes with clinicopathological parameters in endometrial cancer.
    Sana Ahuja, Ashi Dubey, Sufian Zaheer.
       PURPOSE: Endometrial cancer (EC) ranks as one of the most prevalent gynecological malignancies globally. The presence and role of stromal tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment have garnered interest due to their prognostic and therapeutic potential. This study aimed to evaluate the association between stromal TILs and various clinicopathological parameters in EC.
    METHODS: A prospective study was conducted which included 30 histologically confirmed cases of endometrial carcinoma. Specimens collected from January 2023 to June 2024 were processed for routine histopathological examination and immunohistochemistry for CD3 and CD20 markers. TILs were quantified as per the International Immuno-Oncology Biomarker Working Group guidelines and categorized into low (<20%) and high (≥20%) TILs.
    RESULTS: The study comprised 30 female patients, predominantly aged 51 to 60 years. Most tumors were of the endometrioid subtype (93.3%). High TILs were significantly associated with early tumor stage, lower grade, lesser myometrial invasion, and absence of nodal involvement on univariate analysis and with lower tumor stage and grade on multivariate analysis. No significant association was found between TILs and age, lymphovascular, or perineural invasion.
    CONCLUSION: The findings suggest that high TIL infiltration correlates with favorable tumor characteristics, potentially serving as a prognostic marker for early and less aggressive EC. High TILs were associated with better tumor stage, grade, and reduced nodal involvement, indicating their protective role in tumor progression. However, the lack of association with certain parameters calls for further investigation into the functional state of TILs and their interactions within the tumor microenvironment.
    Keywords:  Adenocarcinoma; Endometrial neoplasms; Endometrioid; Tumor infiltrating lymphocytes
    DOI:  https://doi.org/10.14216/kjco.24010
  2. J Cutan Pathol. 2025 Jan 07.
    White Depressed Areas and Tumor Infiltrating Lymphocytes: The Cancer Cure That Lies Within?
    George F Murphy.
      This brief overview is inspired by seminal contributions by the late Dr. Martin C. Mihm, Jr. who provided a basis for recognition and better understanding of interactions between lymphocytes (tumor-infiltrating lymphocytes [TILs]) that home to and permeate cancers. In primary melanomas, this phenomenon may produce what Dr. Mihm called white depressed areas, prescient clues to what would fuel future attempts at harnessing anticancer immunity. The critical and sequential TIL attributes of antigenic stimulation, homing, and effector-target cell apoptotic injury herein are briefly reviewed in light of more recent advances in the field of immuno-oncology. The intent is to emphasize how fundamental clinical and histopathological observations, as forged by Dr. Mihm and his associates, have led to critically important prognostic paradigms as well as to translational insights that now have become transformative in the field of cancer immunotherapy.
    Keywords:  Martin C. Mihm, Jr.; apoptosis; homing; immuno‐oncology; melanoma; tumor‐infiltrating lymphocytes
    DOI:  https://doi.org/10.1111/cup.14768
  3. Clin Transl Oncol. 2025 Jan 09.
    Adoptive cell therapies in thoracic malignancies: a comprehensive review.
    Yago Garitaonaindia, Marta Martínez-Cutillas, Maria Uribarren, Isabel Redondo, Virginia Calvo, Roberto Serna-Blasco, Mariano Provencio.
      This review aims to summarize recent studies and findings within adoptive cell therapies, including tumor-infiltrating lymphocytes, genetically engineered T cell receptors, and chimeric antigen receptor T cells, in the treatment of thoracic malignancies, including non-small cell lung cancer, small cell lung cancer, and malignant pleural mesothelioma. Several trials are ongoing, and a few have reported results, suggesting that adoptive cell therapies may represent a potential treatment option for these patients, especially when checkpoint inhibition has failed. We also discuss the potential implementation of these therapies, as they present a new toxicity profile and an intrinsic financial burden. Despite the challenges to overcome, such as the accurate identification of antigens and developing strategies to improve efficacy and toxicity profiles, new cellular therapies are experiencing significant development in the field of thoracic malignancies.
    Keywords:  Adoptive cell therapies; CAR-T; MPM; NSCLC; SCLC; TCR; Tumor-infiltrating lymphocytes (TILs)
    DOI:  https://doi.org/10.1007/s12094-024-03834-5
  4. J Cancer Res Ther. 2024 Dec 01. 20(7): 1983-1990
    Prognostic value of tumor-infiltrating lymphocyte subtypes and microorganisms in triple-negative breast cancer.
    Yating Shi, Zhi Guo, Qiang Wang, Huan Deng.
       ABSTRACT: Tumor-infiltrating lymphocytes (TILs) are key components of the tumor microenvironment (TME) and serve as prognostic markers for breast cancer. Patients with high TIL infiltration generally experience better clinical outcomes and extended survival compared to those with low TIL infiltration. However, as the TME is highly complex and TIL subtypes perform distinct biological functions, TILs may only provide an approximate indication of tumor immune status, potentially leading to biased prognostic results. Therefore, we reviewed the interactions between immune-infiltrating subtypes and tumor cells throughout the entire TME. By examining the antitumor or protumor effects of each TIL subtype, we aimed to better characterize the tumor immune landscape, offering more accurate and comprehensive insights for guiding triple-negative breast cancer (TNBC) treatment. In addition, this approach could lead to the development of new therapeutic targets, enabling tailored treatment strategies and precision medicine. Accumulating evidence suggests that the intestinal microbiome and its metabolites influence antitumor responses by modulating innate and adaptive immunity, with specific bacteria potentially serving as biomarkers for predicting clinical responses. Various studies have identified microorganisms in breast tissue, previously considered sterile, revealing differences in breast microbial composition between patients with breast cancer and controls, as well as associations between specific breast microorganisms and clinicopathologic features, including immune correlations. The aim of this review was to provide a more comprehensive set of prognostic markers for TNBC and to tap into potential-specific therapeutic targets.
    DOI:  https://doi.org/10.4103/jcrt.jcrt_41_24
  5. Mol Cells. 2025 Jan 06. pii: S1016-8478(25)00001-9. [Epub ahead of print] 100177
    Human γδ T cells in the tumor microenvironment: Key insights for advancing cancer immunotherapy.
    Won Hyung Park, Heung Kyu Lee.
      The role of γδ T cells in antitumor responses has gained significant attention due to their unique major histocompatibility complex (MHC)-independent killing mechanisms, which distinguish them from conventional αβ T cells. Notably, γδ tumor-infiltrating lymphocytes (TILs) have been identified as favorable prognostic markers in various cancers. However, γδ TIL subsets, including Vδ1, Vδ2, and Vδ3, exhibit distinct prognostic implications and phenotypes from one another within the tumor microenvironment (TME). Although the underlying mechanisms remain unclear, recent studies suggest that these subset-specific differences may arise from divergent activation pathways. Vδ1 TILs appear to be mainly activated by γδ T-cell receptor (TCR) signaling, whereas Vδ2 TILs seem to rely on alternative pathways, such as natural killer (NK) receptor-mediated activation. In addition to phenotypic studies, γδ T cell-based immunotherapies are being actively developed using innovative approaches including engineered γδ T cells, γδ T cell engager molecules, and γδ TCR-based T cell therapies. Despite these advancements, challenges such as functional heterogeneity and limited in vivo persistence remain unresolved. Overcoming these obstacles could position γδ T cell therapies as a transformative platform for cancer immunotherapy. This review explores recent findings on the role of γδ T cells as prognostic markers, their phenotypic characteristics within the human TME, and recent advancements in γδ T cell-based cancer immunotherapies, offering valuable insights for the development of novel therapeutic strategies.
    Keywords:  Limitations of γδ T cell therapy; Phenotypic characteristics of γδ T cells; Prognostic value of γδ T cells; γδ T cell-based immunotherapy; γδ tumor-infiltrating lymphocytes
    DOI:  https://doi.org/10.1016/j.mocell.2025.100177
  6. Cureus. 2024 Dec;16(12): e75479
    CD3+ Tumor-Infiltrating Lymphocytes in Breast Carcinoma: Their Prognostic Role and Association With Clinical Parameters.
    Rishav Chauhan, Vijayalaxmi Patil.
      Background Breast carcinoma cases are rising steadily and represent a major cause of mortality and morbidity in India. In response to breast carcinoma, the immune system is activated, resulting in lymphocyte infiltration in and around the tumor nests. This interaction between the tumor and immune system is the basis for studying tumor-infiltrating lymphocytes (TILs). Despite studies on TILs in breast carcinoma, the role of CD3+TILs in predicting patient outcomes remains underexplored. This study aimed to evaluate TILs in breast carcinoma tissues by analyzing CD3 expression through immunohistochemistry (IHC) and examining its association with various prognostic factors, such as histological grade, clinical stage, lymph node status, and hormone receptor status. Methods A study was conducted on 45 breast carcinoma cases, documenting various clinicopathological parameters. IHC staining was performed for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor (HER2-neu), and CD3 markers on tissue samples. Both intra-tumoral and stromal CD3 TILs were quantified and analyzed in relation to clinicopathological prognostic factors. Results In all 45 breast carcinoma cases, intra-tumoral and stromal CD3 expression was assessed. High stromal CD3 expression is documented in the triple-negative breast tumor. CD3 intra-tumoral expression correlated significantly with tumor size (p < 0.035), ER status (p < 0.036), and PR status (p < 0.036). CD3 stromal expression showed no correlation with any of the prognostic parameters.  Conclusion The current study found a strong correlation between CD3 intra-tumoral expression with tumor size, ER and PR status. The findings imply that CD3 may be a significant factor in breast carcinoma prognosis. There were more stromal CD3 TILs in triple-negative breast carcinoma (TNBC) cases. TILs ought to be examined for their capacity as novel prognostic and predictive indicators, especially in cases of invasive breast cancer, such as triple-negative breast carcinoma.
    Keywords:  breast carcinoma; cd3; immunohistochemistry; tumor infiltrating lymphocytes; tumor size
    DOI:  https://doi.org/10.7759/cureus.75479
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