Curr Opin Immunol. 2024 Nov 25;92:102506. doi: 10.1016/j.coi.2024.102506. Online ahead of print.
ABSTRACT
Accumulating evidence demonstrates that tumor-specific CD8+ T cells in tumor-draining lymph nodes (TdLNs) act as an upstream reservoir of exhausted subsets within tumor microenvironment (TME). This reservoir primarily consists of progenitor exhausted CD8+ T (TPEX) cells and newly defined tumor-specific memory subsets (TTSM). We propose that these two subsets work together to mediate the antitumor effects of PD-1/PD-L1 immune checkpoint blockade (ICB) in a spatiotemporal manner. Although PD-1/PD-L1 ICB monotherapy drives the proliferation and further differentiation of these subsets, it does not alter the programmed differentiation trajectory from TTSM cells to TPEX cells, ultimately leading to the development of terminally exhausted CD8+ T cells. This phenomenon may partly explaining the frequent relapse in patients following initial ICB therapy. In this review, we focus on the phenotypic and functional heterogeneity of tumor-specific CD8+ T cells in both TdLNs and the TME and discuss the implications of these studies for ICB. Our insights aim to illuminate new strategies for advancing tumor immunotherapies.
PMID:39591663 | DOI:10.1016/j.coi.2024.102506