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- W3091949069 endingPage "188447" @default.
- W3091949069 startingPage "188447" @default.
- W3091949069 abstract "Colorectal cancers (CRCs) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) often have sustained responses to immune checkpoint inhibitors (ICIs) including selective monoclonal antibodies against Program Death 1 (PD-1), Programmed Death Ligand 1(PD-L1), and cytotoxic T lymphocyte associated antigen 4 (CTLA-4). However, a substantial fraction of dMMR CRCs do not respond or ultimately develop resistance to immunotherapy. The majority (~85%) of CRCs are MMR proficient (pMMR) or microsatellite stable (MSS) and lack response to ICIs. Understanding the biology and mechanisms underlying dMMR-associated immunogenicity is urgently needed for improving the therapeutic efficacy of immunotherapy on CRC. Compared to pMMR/MSS CRCs, dMMR/MSI CRCs typically have increased tumor mutational burden (TMB), lower response rate to 5-fluorouracil-based chemotherapy, distinctive immunological features such as high tumor-infiltrating lymphocytes (TILs), and better prognosis. Here, we review the current understanding of the clinical relevance of dMMR/MSI in CRCs, the molecular basis and rationales for targeting dMMR CRC with immunotherapy, and clinical approaches using ICIs as single agents or in combination with other therapies for MSI-H CRCs. Furthermore, we address the potential strategies to sensitize pMMR/MSS CRC to immunotherapy by converting an immunologically “cold” microenvironment into a “hot” one." @default.
- W3091949069 created "2020-10-15" @default.
- W3091949069 creator A5001788888 @default.
- W3091949069 creator A5028319181 @default.
- W3091949069 creator A5028963094 @default.
- W3091949069 creator A5034979524 @default.
- W3091949069 creator A5067031550 @default.
- W3091949069 creator A5086910766 @default.
- W3091949069 date "2020-12-01" @default.
- W3091949069 modified "2023-10-18" @default.
- W3091949069 title "Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside" @default.
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