Different tumor-resident memory T cells promote responses to different cancer immunotherapies 2110

Abstract Description The accumulation of CD103+CD8+ resident memory T (TRM) cells in tumors is predictive of a response to PD-1 blockade immunotherapy. However, the nature of TRM cells regulating responses to other immune checkpoint inhibitors (ICI) and therapeutic cancer vaccines remains unclear. Using mouse tumor models, we show here that CD103+CD8+ TRM cells promote responses to a melanoma peptide vaccine and to anti-PD-1 neutralizing antibodies, whereas the response to anti-CTLA-4 antibodies requires a CD4+ TRM subset. Benefits of the cancer vaccine and anti-PD-1 therapy, but not of anti-CTLA-4 therapy, are compromised in mice challenged with anti-CD8 and anti-CD103 blocking antibodies, and in CD103-knockout mice, unless wild-type CD8+ T cells are also transferred. Tumor growth control in vaccinated mice is associated with a decrease in the percentage of intra-tumoral Tcf-1+CD103+CD8+ TRM-like cells and an expansion of CD8+ effector-like T cells. A combination of the TrackSOM algorithm applied to spectral cytometry and T-cell receptor (TCR) sequencing in CD8+ tumor-infiltrating T lymphocytes (TIL) showed that immunotherapy induces the differentiation of Tcf-1+CD103+ TRM-like cells into effector-like T cells, controlling tumor progression. These results support the conclusion that targeting tumor stem-like CD8+ T-cell progenitors to promote TRM formation may improve cancer immunotherapy efficacy. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)