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  • Title: The primordial differentiation of tumor-specific memory CD8+ T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes.
    Author: Huang Q, Wu X, Wang Z, Chen X, Wang L, Lu Y, Xiong D, Liu Q, Tian Y, Lin H, Guo J, Wen S, Dong W, Yang X, Yuan Y, Yue Z, Lei S, Wu Q, Ran L, Xie L, Wang Y, Gao L, Tian Q, Zhou X, Sun B, Xu L, Tang Z, Ye L.
    Journal: Cell; 2022 Oct 27; 185(22):4049-4066.e25. PubMed ID: 36208623.
    Abstract:
    Blocking PD-1/PD-L1 signaling transforms cancer therapy and is assumed to unleash exhausted tumor-reactive CD8+ T cells in the tumor microenvironment (TME). However, recent studies have also indicated that the systemic tumor-reactive CD8+ T cells may respond to PD-1/PD-L1 immunotherapy. These discrepancies highlight the importance of further defining tumor-specific CD8+ T cell responders to PD-1/PD-L1 blockade. Here, using multiple preclinical tumor models, we revealed that a subset of tumor-specific CD8+ cells in the tumor draining lymph nodes (TdLNs) was not functionally exhausted but exhibited canonical memory characteristics. TdLN-derived tumor-specific memory (TTSM) cells established memory-associated epigenetic program early during tumorigenesis. More importantly, TdLN-TTSM cells exhibited superior anti-tumor therapeutic efficacy after adoptive transfer and were characterized as bona fide responders to PD-1/PD-L1 blockade. These findings highlight that TdLN-TTSM cells could be harnessed to potentiate anti-tumor immunotherapy.
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