Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer

Abstract

Objective: This study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.

Methods: Using single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.

Results: A total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8⁺T_RM was positively correlated with CD8⁺IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+T_N and CD4+blood-T_CM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8⁺IEL cells were found in rectal cancer but not in colon cancer, while CD8⁺ T_N cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8⁺ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.

Conclusions: We characterized the T cell populations in the CRC tumor tissue and peripheral blood.

Keywords: colon cancer; immunotherapy; rectal cancer; single-cell RNA sequencing; tumor-infiltrating T cells.