Journal article
Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside
Biochimica et biophysica acta. Reviews on cancer, Vol.1874(2), pp.188447-188447
12/01/2020
DOI: 10.1016/j.bbcan.2020.188447
PMCID: PMC7886024
PMID: 33035640
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 (similar to 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 MSIH CRCs. Furthermore, we address the potential strategies to sensitize pMMR/MSS CRC to immunotherapy by converting an immunologically "cold" microenvironment into a "hot" one.
Details
- Title: Subtitle
- Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside
- Creators
- Darleny Y. Lizardo - University of PittsburghChaoyuan Kuang - University of PittsburghSuisui Hao - University of PittsburghJian Yu - University of PittsburghYi Huang - University of PittsburghLin Zhang - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Reviews on cancer, Vol.1874(2), pp.188447-188447
- DOI
- 10.1016/j.bbcan.2020.188447
- PMID
- 33035640
- PMCID
- PMC7886024
- NLM abbreviation
- Biochim Biophys Acta Rev Cancer
- ISSN
- 0304-419X
- eISSN
- 1879-2561
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- R01CA203028; R01CA217141; R01CA236271; R01CA247231; U19AI068021; R01CA215481; T32CA193205; P30CA047904 / U.S. National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/01/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383913302771
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