The evolving role of immune oncology in colorectal cancer

Metastatic colorectal cancer still remains an essentially non curable disease. However, with advances in chemotherapeutic and personalizing therapeutic approaches with the incorporation of targeted therapy such as anti-EGFR and anti-VEGF agents survival associated with metastatic colorectal cancer has certainly improved over the last two decades. Patients who are not amenable to surgery median survival remain approximately 2 to 3 years. In an attempt to improve prognostic outcome over the last decade research has focused on therapeutic options geared towards harnessing the immune system with success observed with the use of immune checkpoint inhibitors in the real of a number of solid tumors including lung and renal cancer. The use of immunomodulatory therapeutic approaches for the management of unselected advanced colorectal cancer has not seen the same success with low response rates reported. The turning point was our recent understanding that efficacy of immunotherapy was limited to a subset of patients with hyper mutated microsatellite instability-high (MSI-H) tumors. This review will focus on summarizing available knowledge on the immunological and molecular landscape of colorectal cancer that can help determine subsets of immunogenic CRC, determine potential predictive markers to help select patients for immunotherapeutic approaches as well looking at the existing evidence of incorporating immune checkpoint inhibitors to the therapeutic management of patients with mCRC.