Incorporation of Combination Immunotherapy into the Treatment Paradigms of Gastrointestinal Cancers

Immune checkpoint inhibitors allow innate immune cells to recognize and attack tumour cells by removing inhibitory signals associated with tumours and their microenvironment. These agents can induce durable responses and they have transformed the management of many cancer types. There have been great efforts to incorporate immunotherapy (IO) into the treatment of gastrointestinal (GI) cancers. However, most of the GI cancers, except for microsatellite unstable tumours, are largely resistant to IO, especially when used as monotherapy. Increased efficacy has been observed when these agents are combined with other drugs, including chemotherapy, other immune checkpoint inhibitors, or targeted drugs. This review will summarize recent advances in the management of GI cancers with the incorporation of immune checkpoint inhibitors into current treatment paradigms. It will review pivotal studies that led to these practice updates and highlight potentially practice-changing ongoing clinical studies that involve IO agents.