Vaccines and immune checkpoint inhibitors: a promising combination strategy in gastrointestinal cancers
Abstract
Cancer immunotherapy with traditional immune checkpoint inhibitors (ICIs) has seen limited success across gastrointestinal (GI) tumors, including adenocarcinomas of colon and rectum, esophagus, stomach and pancreas. The benefit of ICIs has been confined to GI tumors with mismatch repair deficiency (dMMR) or, recently, high tumor-mutational burden (TMB). Unfortunately, some dMMR/TMBhi patients receive little benefit from ICIs, while the majority of GI cancers have proficient mismatch repair and low TMB status, limiting the overall benefit to the GI cancer patient population. Over the last several years, numerous combinations of novel checkpoint targets, chemotherapy or targeted therapies have been investigated to convert the immunologically ‘cold’ (proficient mismatch repair, TMBlo) GI tumors into hot, inflammatory tumors to recapitulate the benefit seen in dMMR or TMBhi subsets. While there have been some successes, there remains significant unmet need to find novel immuno-oncology combinations. Here, we discuss this emerging paradigm and novel opportunities to enhance the efficacy of the immune system in its fight against GI cancers.
