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Optimizing immunotherapy for colorectal cancer

Important colorectal cancer (CRC) studies in 2021, including a new standard of care for first-line treatment of MSI-H–dMMR metastatic CRC, single-cell and spatial analysis of primary tumours and investigations of diet in preclinical models of cancer initiation, have provided novel insights into the CRC immune microenvironment.

Key advances

  • Pembrolizumab (an anti-PD1 monoclonal antibody) has been established as the new standard of care for first-line treatment of metastatic microsatellite-high–mismatch repair-deficient colorectal cancer4.

  • Comprehensive single-cell and spatial analyses of patient samples have identified distinct multicellular immune modulatory hubs in mismatch repair-deficient and mismatch repair-proficient primary colon tumours9.

  • High-fat diet can cause microbiome-dependent downregulation of MHC class II expression on LGR5+ intestinal stem cells in mice, in turn enabling immune evasion and promoting intestinal tumorigenesis10.

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Fig. 1: Modulating the local and systemic immune microenvironment of colorectal cancer.


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K.G. is supported by NIH grants K08 CA230213, U2C CA233284 and P30 CA 008748, a Damon Runyon Clinical Investigator Award, Burroughs Wellcome Career Award for Medical Scientists, AACR NextGen Grant for Transformative Cancer Research, Josie Robertson Investigator Award and a Stand Up To Cancer Convergence Award.

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Correspondence to Karuna Ganesh.

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Ganesh, K. Optimizing immunotherapy for colorectal cancer. Nat Rev Gastroenterol Hepatol 19, 93–94 (2022).

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