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Abstract
The introduction of immunotherapy in the treatment of metastatic colorectal cancer (CRC) has revolutionized this and many other areas of oncology, with up to 30-40 % of patients with incurable disease eligible for immune checkpoint inhibitors (ICIs) achieving durable responses. Until recently, the administration of immunotherapy in CRC depended on a binary molecular/immunohistochemical predictor: the presence or absence of microsatellite instability/mismatch DNA repair deficiency (dMMR) in metastatic CRC. Currently, the potential applications of ICI in CRC are expanding rapidly. For example, their efficacy has been demonstrated in the neoadjuvant setting and in cases with hereditary and somatic mutations in the DNA polymerases POLE/POLD1. A tremendous amount of research has been done to characterize the biological role and clinical significance of tumor mutational burden, individual driver mutations, tumor cell expression characteristics, tumor microenvironment, systemic immunity, etc. This review aims to highlight the current understanding of the role and mechanisms of influence of high mutational tumor burden, either related or unrelated to microsatellite instability/dMMR, on the effect of immunotherapy.
References
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