Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer

Clinical outcomes in colorectal cancer (CRC) correlate with T cell infiltrates, but the specific contributions of heterogenous I cell types remain unclear. To investigate the diverse function of T cells in CRC, we profiled 37,931 T cells from tumors and adjacent normal colon of 16 patients with CRC with respect to transcriptome, TCR sequence, and cell surface markers. Our analysis identified phenotypically and functionally distinguishable effector T cell types. We employed single-cell gene signatures from these T cell subsets to query the TCGA database to assess their prognostic significance. We found 2 distinct cytotoxic T cell types. GZMK(+)KLRG1(+) cytotoxic T cells were enriched in CRC patients with good outcomes. GNLY(+)CD103(+) cytotoxic T cells with a dysfunctional phenotype were not associated with good outcomes, despite coexpression of CD39 and CD103, markers that denote tumor reactivity. We found 2 distinct Treg subtypes associated with opposite outcomes. While total Tregs were associated with good outcomes, CD38(+) Tregs were associated with bad outcomes independently of stage and possessed a highly suppressive phenotype, suggesting that they inhibit antitumor immunity in CRC. These findings highlight the potential utility of these subpopulations in predicting outcomes and support the potential for novel therapies directed at CD38(+) Tregs or CD8(+)CD103(+) T cells.

Automated summary

This study identified distinct subsets of T cells in colorectal cancer, including cytotoxic T cells associated with good outcomes (GZMK(+)KLRG1(+)) and dysfunctional cytotoxic T cells associated with poor outcomes (GNLY(+)CD103(+)). Additionally, CD38(+) Tregs were associated with bad outcomes and inhibitory effects on antitumor immunity. These findings suggest the potential utility of these T cell subsets in predicting outcomes and the possibility of novel therapies targeting specific T cell populations.