Colorectal cancer: A paradigmatic model for cancer immunology and immunotherapy

Abstract

Colorectal cancer can be categorized into two major molecular subtypes according to the status of their DNA proofreading and repair machinery. The DNA repair status of tumor cells plays a major role in shaping the immune landscape of tumors and in determining the clinical response of colorectal cancer patients to immune checkpoint blockade therapies. Colorectal cancers that develop in a context of DNA mismatch repair or polymerase proofreading deficiency are generally conspicuously infiltrated by effector memory T cells and are associated with an improved clinical prognosis relative to their replication repair-proficient counterpart. While mismatch repair-deficient colorectal cancers, and most likely POLE and POLD1-mutated cancers, are amenable to immune checkpoint blockade therapies, the promise of immunotherapy still remains unfulfilled for for the majority of colorectal cancer patients. This review focusses on the role of the immune system in the tumorigenesis and clinical behavior of colorectal cancer. Furthermore, we discuss how latest advances in the fields of genomics and oncoimmunology may pave the way to broaden the scope of immunotherapy for this disease.

Keywords: Checkpoint blockade; Colorectal cancer; Immunotherapy; Mismatch repair; Neoantigens; Tumor infiltrating lymphocytes.