bims-tumhet 2025-11-16 papers

Issue of 2025–11–16
seven papers selected by
Sergio Marchini, Humanitas Research

J Hematol Oncol. 2025 Nov 11. 18(1): 97

Tertiary lymphoid structures in cancer: spatiotemporal heterogeneity, immune orchestration, and translational opportunities.

Shuxuan Deng, Yanjie Chen, Bin Song, Heng Wang, Shanshan Huang, Kongming Wu, Qian Chu.

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates that form in or in close proximity to tumors and other chronically inflamed tissues, where they serve as crucial sites for local antigen presentation, lymphocyte priming, and adaptive immune coordination. Increasing evidence across diverse cancers supports TLSs as key modulators of antitumor immunity, correlating with improved patient prognosis and response to immune checkpoint blockade. Yet, TLSs exhibit striking spatiotemporal and functional heterogeneity-ranging from immune-stimulatory to immune-suppressive-which complicates their clinical interpretation and therapeutic targeting. Recent studies have focused on elucidating the molecular cues driving TLS induction, the mechanisms regulating their maturation, and their dynamic interactions with the tumor microenvironment. In this review, we provide an integrated overview of these advances and discuss the clinical and translational implications of TLSs as prognostic biomarkers and immunotherapeutic targets.

Keywords: Immunotherapy; Prognostic biomarkers; Spatial heterogeneity; TLS-targeted strategies; Tertiary lymphoid structures; Tumor microenvironment

DOI: https://doi.org/10.1186/s13045-025-01754-7

J Gynecol Oncol. 2025 Oct 10.

Adjuvant treatment algorithm based on recent ESGO/ESTRO/ESP guidelines for early endometrial carcinoma according to prognostic risk groups.

Jean-Francois Baurain, Carine Kirkove, Aline Francois, Gwenael Ferron, Mathieu Luyckx.

The incidence of endometrial cancer (EC) is unfortunately increasing. Often diagnosis is made at an early stage and surgery is the curative treatment. Nevertheless, adjuvant treatment is proposed to reduce the risk of relapse. This treatment is tailored based on the extent of the disease, such as the presence of distant metastasis, the extent of involvement of adjacent organs or lymph nodes. However, histological parameters such as myometrial invasion, substantial lymphovascular space invasion, invasion of the cervical stroma or tumor grade are also key to selecting adjuvant treatment. The Cancer Genome Atlas (TCGA) project has demonstrated the superiority of molecular classification over histological evaluation in EC to determine the prognosis. The International Federation of Gynecology and Obstetrics 2023 staging for EC is the first staging system that has incorporated molecular biomarkers on top of morpho-histological classification. Currently, all patients should have a molecular profile of their tumor and a lymph node assessment. The landmark treatment of stage I-III ECs is surgery followed by radiotherapy. The European guidelines updated in 2025 has divided EC in 4 risk categories with specific adjuvant treatment. For clinicians, it is seen as a complex landscape from surveillance to chemo-radiotherapy. Therefore, we propose here a practical pocket guideline for adjuvant treatment of early-stage EC patients based on a review of the different clinical trials in the adjuvant setting and on existing guidelines. This pocket guideline may also serve as a base for incorporation of new clinical trials under the RAINBO umbrella research program.

Keywords: Chemotherapy; Endometrial Cancer; Immunotherapy; Radiotherapy

DOI: https://doi.org/10.3802/jgo.2026.37.e28

Bioinform Adv. 2025 ;5(1): vbaf236

FinaleToolkit: accelerating cell-free DNA fragmentation analysis with a high-speed computational toolkit.

James Wenhan Li, Ravi Bandaru, Kundan Baliga, Yaping Liu.

Motivation: Cell-free DNA (cfDNA) fragmentation pattern represents a promising non-invasive biomarker for disease diagnosis and prognosis. Numerous fragmentation features, such as end motif and window protection score (WPS), have been characterized in cfDNA genomic sequencing. However, the analytical tools developed in these studies are often not released to the liquid biopsy community or are inefficient for genome-wide analysis in large datasets.
Results: To address this gap, we have developed FinaleToolkit, a fast and memory-efficient Python package designed to generate comprehensive fragmentation features from large cfDNA genomic sequencing data. For instance, FinaleToolkit can generate genome-wide WPS features from a ∼100× cfDNA whole-genome sequencing (WGS) dataset with over 1 billion fragments in 0.7 h, offering up to a ∼50-fold increase in processing speed compared to original implementations in the same dataset. We have benchmarked FinaleToolkit against original approaches or implementations where possible, confirming its efficacy. Furthermore, FinaleToolkit enabled the genome-wide analysis of fragmentation patterns over arbitrary genomic intervals, significantly boosting the performance for cancer early detection.
Availability and implementation: FinaleToolkit is open source and thoroughly documented with both command line interface and Python application programming interface (API) to facilitate its widespread adoption and use within the research community: https://github.com/epifluidlab/FinaleToolkit.

DOI: https://doi.org/10.1093/bioadv/vbaf236

Mol Oncol. 2025 Nov 14.

Methylation biomarkers can distinguish pleural mesothelioma from healthy pleura and other pleural pathologies.

Janah Vandenhoeck, Nele De Meulenaere, Thomas Vanpoucke, Joe Ibrahim, Dieter Peeters, Suresh Krishan Yogeswaran, Wen Wen, Paul Van Schil, Jeroen M H Hendriks, Jo Raskin, Jan van Meerbeeck, Guy Van Camp, Ken Op de Beeck.

Pleural mesothelioma (PM) is a rare and aggressive cancer that often requires multiple diagnostic procedures before a definitive diagnosis can be made. To improve diagnostic accuracy, we developed a DNA methylation-based biomarker assay capable of distinguishing PM from healthy pleura and other pleural pathologies. Using Infinium EPIC array data, we identified 744 hypermethylated CpG sites in PM as candidate biomarkers. These were validated in silico using external datasets, yielding a high mean AUC of 0.935. Clinical validation was performed using IMPRESS, a novel bisulfite-free methylation detection technique that enables simultaneous analysis of thousands of CpG sites. A two-step classifier approach was applied: the first model differentiated tumoral from nontumoral pleura with 89.2% sensitivity and 93.5% specificity, while the second model distinguished PM from pleural metastases with 85.2% sensitivity and 100% specificity. These results demonstrate that our methylation-based biomarker panel offers a highly accurate and minimally invasive tool for differentiating PM from other pleural conditions, potentially streamlining the diagnostic process and improving clinical decision-making.

Keywords: DNA methylation; cancer biomarkers; pleural mesothelioma

DOI: https://doi.org/10.1002/1878-0261.70159

Trends Cancer. 2025 Nov 07. pii: S2405-8033(25)00252-3. [Epub ahead of print]

Mechanisms of whole-genome doubling in cancer evolution.

Connor D McKenney, Sergi Regot.

Whole-genome doubling (WGD) has recently emerged as one of the most common genomic alterations in cancer and is associated with genomic instability, drug resistance, and metastasis. However, WGD also generates unique vulnerabilities that create a therapeutic window between cancer cells and healthy cells. Over the past few years, there has been a rapid growth in our understanding of WGD at a molecular level. In this review, we discuss the causes and immediate cellular effects of, and therapeutic considerations for, WGD in cancer.

Keywords: WGD; cytokinesis failure; endoreplication; mitotic slippage; ploidy-specific lethality; tetraploid

DOI: https://doi.org/10.1016/j.trecan.2025.10.001