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

Karlsen, V. T.; Majid, U.; Lindholm, H. T.; Umu, S. U.; Vander-Elst, K. R.; Beitnes, A.-C. R.; Merok, M. A.; Hagen, K. T.; Nilsen, H. R.; Yaqub, S.; Baekkevold, E. S.; Domanska, D.; Jahnsen, F. L.

2025-04-03 cancer biology
10.1101/2025.03.31.646286 bioRxiv
Show 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.

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