Single cell spatial transcriptomics identifies coordinated cellular programs associated with good prognosis in microsatellite stable colorectal cancer

Abstract

It has been reported that microsatellite instable (MSI) tumors in colorectal cancer (CRC) exhibit stronger anti-tumor responses than microsatellite stable (MSS) tumors. Analyzing scRNA-seq data from 185 CRC patients we found that immune, structural, and cancer cells in MSS tumors with high numbers of tumor-infiltrating CD8 T cells and macrophages (TAMs; CD8hiTAMhi) and CD8lowTAMhi tumors were enriched for pathways associated with anti- and pro-tumor responses, respectively. In CD8hiTAMhi tumors, TAMs expressed an IFN-induced phenotype (e.g. GBP1, CXCL9, IFITM3) and high infiltration of GBP1+ TAMs was associated with better overall survival (n=941). High-resolution spatial transcriptomics (Visium HD) revealed that GBP1+ TAMs clustered with CXCL13+IFNG+PDCD1+ CD8 T cells in tumoral niches, suggesting that GBP1+ TAMs were involved in recruitment and activation of tumor-reactive CD8 T cells. Together, we uncovered coordinated cellular programs across cell types in the microenvironment of MSS tumors, based on simple classification variables, that were strongly associated with prognosis.