| First Author | Huang Q | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 22 | Pages | 4049-4066.e25 |
| PubMed ID | 36208623 | Mgi Jnum | J:336854 |
| Mgi Id | MGI:7378106 | Doi | 10.1016/j.cell.2022.09.020 |
| Citation | Huang Q, et al. (2022) The primordial differentiation of tumor-specific memory CD8(+) T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes. Cell 185(22):4049-4066.e25 |
| abstractText | 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. |
