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Abstract
High-level microsatellite instability (MSI-H) is a major predictive marker of response to immunotherapy in patients with colorectal cancer (CRC). Despite its apparent utility, it does not accurately predict long-term benefit from immune checkpoint inhibitors (ICIs): up to half of patients with metastatic MSI-H CRC demonstrate primary or acquired resistance to therapy. Meanwhile, immunotherapy may be beneficial even in the absence of MSI-H. Considerable research effort has been devoted to identifying additional factors associated with response to ICI and finding ways to induce sensitivity to this type of treatment. This review summarizes the accumulated evidence and emerging trends in the study of factors that determine the success of immunotherapy. In particular, the importance of characteristics of the tumor microenvironment, including the subpopulation composition of the immune infiltrate; inherited and acquired characteristics of immune system function; the role of somatic mutations in various molecular signaling cascades; the role of the intestinal microbiome, etc. are discussed.
References
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