Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm

Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with MMR-D/MSI-H genotype often carry a higher tumor mutation burden frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen immune (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in rapid development these novel therapeutics within landscape MSI-H cancers. Recently, several clinical trials utilized ICIs as potential neoadjuvant therapies for cancers and demonstrated deep pathological responses, creating opportunities organ preservation. However, there challenges use certain disease types due risk overtreatment that can be cured through surgery-only approach. In this review article, we discuss approaches ICI therapy patients including those oligometastatic disease. We also elaborate on utilization provide further insight into changing treatment paradigm