CD8+ T cells in breast cancer tumors and draining lymph nodes: PD-1 levels, effector functions and prognostic relevance

CD8+ T cells in breast cancer tumors and draining lymph nodes: PD-1 levels, effector functions and prognostic relevance

CD8+ T cells shape the antitumor immune response. Here, we evaluated CD8+ T cells expressing different levels of PD-1, their functional status, and distribution in different tissues of luminal breast cancer (BC) patients. We characterized the exhaustion stages of CD8+ T cells in tumors, juxtatumoral...

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Main Authors: Carolina Abrate, Fernando P. Canale, Sabrina N. Bossio, Jimena Tosello Boari, María C. Ramello, Nicolas Nuñez, Wilfrid Richer, Christine Sedlik, Jordan Denizeau, Anne Vincent-Salomon, Edith Borcoman, Andres Del Castillo, Adriana Gruppi, Eva V. Acosta Rodríguez, Eliane Piaggio, Carolina L. Montes
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
Subjects:
Breast cancer
CD8+ T cells
exhaustion
PD-1
draining lymph nodes
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2502354
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Summary:CD8+ T cells shape the antitumor immune response. Here, we evaluated CD8+ T cells expressing different levels of PD-1, their functional status, and distribution in different tissues of luminal breast cancer (BC) patients. We characterized the exhaustion stages of CD8+ T cells in tumors, juxtatumoral tissues (JTs), and tumor-draining lymph nodes (TDLNs). Terminal exhausted CD8+ T cells (PD-1High CD8+) were predominant in tumors and nearly absent in other tissues. However, in all tissues evaluated, most CD8+ T cells exhibited a pre-exhausted phenotype (PD-1Int CD8+) or did not express PD-1. PD-1High and PD-1Int CD8+ T cells from tumors and JTs presented central and effector memory phenotypes, while in TDLNs were primarily central memory. TCR-β sequencing revealed higher clonality among CD8+ T cells from tumor than TDLNs, with tumor-enriched clones also detected in TDLNs. Analysis of scRNA-seq datasets from tumors and JTs of colorectal and non-small cell lung cancer patients, identified a CD8+ terminal exhaustion and a CD8+ pre-exhausted signatures. High expression of exhaustion-associated genes in BC tumors correlated with improved overall survival. Overall, PD-1 expression effectively distinguishes exhaustion stages in CD8+ T cells. PD-1Int cells found in tumors, JTs, and TDLNs represent a promising therapeutic target for cancer immunotherapy.
ISSN:2162-402X

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