乳腺癌肿瘤和引流淋巴结中的 CD8(+) T 细胞：PD-1 水平、效应功能及预后相关性

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-1 High 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-1 Int CD8 + ) or did not express PD-1. PD-1 High and PD-1 Int 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-1 Int cells found in tumors, JTs, and TDLNs represent a promising therapeutic target for cancer immunotherapy.