The functional and phenotypic diversity of single T-cell infiltrates in human colorectal cancer as correlated with clinical outcome

Although degree of T-cell infiltration in CRC was shown to correlate with a positive prognosis, the contribution of phenotypically and functionally distinct T cell subtypes within tumors remains unclear. We analyzed 37,931 single T cells with respect to transcriptome, TCR sequence and 23 cell surface proteins, from tumors and adjacent normal colon of 16 patients. Our comprehensive analysis revealed two phenotypically distinct cytotoxic T cell populations within tumors. Its main population transitioned from one positively prognostic effector memory to the other non-prognostic resident memory population in a stage-dependent manner. We further defined several Treg subpopulations within tumors. While Tregs overall were associated with positive clinical outcomes, the CD38+ peripherally-derived Treg subpopulation, phenotypically related to Th17 cells, correlated with poor outcomes independent of cancer stage. Thus, we demonstrated the prognostic significance of single CD8+ and CD4+ T-cell infiltrates in CRC, which could inform therapeutic strategies.