The development of immune checkpoint inhibitors (ICIs) targeting cytotoxic Tlymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), orprogrammed cell death protein ligand 1 (PD-L1) has revolutionized the treatmentstrategy in various types of cancers. In addition, recent studies have revealedthat tumor microsatellite instability (MSI) status and tumor mutation burden(TMB) contribute significantly to the therapeutic response to anti-PD-1monoclonal antibody (mAb), which led to an accelerated approval to pembrolizumabfor the treatment of MSI-high or mismatch-repair-deficient solid tumors afterconventional chemotherapies in 2017 and for the treatment of TMB-high solidtumors in 2020 by the United States Food and Drug Administration (FDA). In thefield of gastrointestinal cancers, many clinical trials evaluating the safetyand efficacy of various regimens such as ICI monotherapy, the combination ofanti-CTLA-4 mAb and anti-PD-1/PD-L1 mAb, and combination of ICI and conventionalchemotherapy or tyrosine kinase inhibitor have been reported or are in progress.This review summarizes MSI status and TMB in gastrointestinal, hepatobiliary,and pancreatic cancers, and provides the results of most relevant clinicaltrials evaluating ICIs. We also discuss the development of biomarkers requiredfor improving the selection of patients with a high probability of benefitingfrom treatment with ICIs, and potential therapeutic strategies that could helpto enhance anticancer responses of ICIs.
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