ArticleBreast cancer research : BCR2016
An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers.
Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 4 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Prognostic significance of CD8 + tumor-infiltrating lymphocytes in operable breast cancer: a meta-analysis.BMC cancer · 2025Pooled it
- The prognostic values of FOXP3Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Pooled it
- Pooled it
- Prognostic Value of Lymphocyte-Activation Gene 3 (LAG3) in Cancer: A Meta-Analysis.Frontiers in oncology · 2019Pooled it
- Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis.Journal for immunotherapy of cancer · 2018Trial
- Advancements in Immune Checkpoint-Based Immunotherapy for Triple-Negative Breast Cancer.Current issues in molecular biology · 2026Review
- Quantitative proteomics analysis of triple-negative breast cancers.NPJ precision oncology · 2025Article
- Baseline sLAG-3 levels in Caucasian and African-American breast cancer patients.Breast cancer research and treatment · 2024Article
- Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Article
- Using random forests to uncover the predictive power of distance-varying cell interactions in tumor microenvironments.PLoS computational biology · 2024Article
- Improving efficacy of TNBC immunotherapy: based on analysis and subtyping of immune microenvironment.Frontiers in immunology · 2024Review
- Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review.Frontiers in immunology · 2024Review
- Prognostic significance of Lymphocyte-activation gene 3 (LAG3) in patients with solid tumors: a systematic review, meta-analysis and pan-cancer analysis.Cancer cell international · 2023Review
- Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma.Journal of ovarian research · 2023Article
- Article
- Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer.International journal of molecular sciences · 2023Review
- Review
- LAG-3 expression in tumor microenvironment of triple-negative breast cancer.Turkish journal of medical sciences · 2023Article
- Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy.Frontiers in pharmacology · 2023Review
- Hypoxia: syndicating triple negative breast cancer against various therapeutic regimens.Frontiers in oncology · 2023Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC.
methodsFormalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259). Results were validated in an independent cohort of patients with TNBC (n = 104). Stromal TILs were evaluated on hematoxylin-and-eosin-stained sections. The density of CD4+, CD8+, and FOXP3+ lymphocytes, and the expression of the immune checkpoints PD-1 and LAG-3, were assessed by immunohistochemical analysis.
resultsThe presence of elevated TILs positively correlated with the density of all T cell subtypes, especially cytotoxic CD8+ lymphocytes. We showed that increasing stromal TILs assessed as a continuous variable is an independent prognostic marker of prolonged relapse-free survival and overall survival in TNBC. Among immune subpopulations, CD8+ lymphocytes are the main effectors of anti-tumor immune responses. In two independent cohorts, we found that PD-1 and LAG-3 were concurrently expressed in approximately 15% of patients with TNBC. The expression of both checkpoint receptors positively correlated with the presence of TILs, but was not significantly associated with patient outcome.
conclusionsOverall, our data indicate that the evaluation of stromal TILs remains the most reliable immune prognostic marker in TNBC, and support the clinical evaluation of anti-PD-1/PD-L1 and anti-LAG-3 in a subset of patients with TNBC who have concurrent expression of both checkpoint receptors.
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