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

Masuda, K.; Kornberg, A.; Lin, S.; Ho, P.; Secener, K.; Suek, N.; Bacarella, A. M.; Ingham, M.; Rosario, V.; Al-Masrou, A. M.; Lee-Kong, S. A.; Kiran, P. R.; Yan, K. S.; Stoeckius, M.; Smibert, P.; Oberstein, P. E.; Sims, P. A.; Han, A.

2020-09-28 immunology
10.1101/2020.09.27.313445 bioRxiv
Show abstract

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, including positively prognostic effector memory cells and non-prognostic resident memory cells. These cytotoxic T cell infiltrates transitioned from effector memory to resident memory in a stage-dependent manner. We further defined several Treg subpopulations within tumors. While Tregs overall were associated with positive clinical outcomes, CD38+ peripherally-derived Tregs, phenotypically related to Th17 cells, correlated with poor outcomes independent of cancer stage. Thus, our data highlight the diversity of T cells in CRC and demonstrate the prognostic significance of distinct T cell subtypes, which could inform therapeutic strategies.

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