Resolving the difference between left-sided and right-sided colorectal cancer by single-cell sequencing.

peer reviewedColorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways, and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells from 3 left-sided and 3 right-sided CRC patients were profiled by single-cell RNA-Seq (scRNA-Seq). Right-sided CRC harbors a significant proportion of exhausted CD8+ T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of preexhausted/exhausted T cells were favorable prognostic markers. Notably, we identified a potentially novel RBP4+NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC