黑色素瘤和鳞状细胞癌 TIL 区室的转录评估揭示耗竭与功能性 T 细胞的意外谱系

To investigate mechanisms associated with terminally exhausted T cells, we sorted and performed transcriptional profiling of CD8 + tumor-infiltrating lymphocytes (TILs) co-expressing the exhaustion markers PD-1 and TIM-3 from large-volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single-cell level, to identify potential mechanisms that underlie their dysfunctional phenotype.

We identified novel dysregulated pathways in CD8 + PD-1 + TIM-3 + cells that have not been well studied in TILs; these include bile acid and peroxisome pathway-related metabolism and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression. DISCUSSION: Based on bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma.