Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

Abstract

Colorectal cancer (CRC) is one of the most common diseases in the world. Tumor immunotherapy is an innovative cancer treatment that acts by activating the human body's autoimmune system. Immune checkpoint block has been shown to be effective in DNA deficient mismatch repair/microsatellite instability-high CRC. However, the therapeutic effect for proficient mismatch repair/microsatellite stability patients still requires further study and optimization. At present, the main CRC strategy is to combine other therapeutic methods, such as chemotherapy, targeted therapy, and radiotherapy. Here, we review the current status and the latest progress of immune checkpoint inhibitors in the treatment of CRC. At the same time, we consider therapeutic opportunities for transforming cold to hot, as well as perspectives on possible future therapies, which may be in great demand for drug-resistant patients.

Keywords: DNA mismatch repair; PD-1/PD-L1; colorectal cancer; combination therapy; immune checkpoint inhibitors.

Figure 1

Immunological checkpoints and combination therapies of CRC. The mismatch repair (MMR)/microsatellite instability (MSI) system is the most important indicator for CRC classification. ICIs have a significant effect in patients with dMMR/MSI-H who can benefit from them.The pMMR/MSS population has no obvious benefits due to its inherent immunosuppressive characteristics, low tumor lymphocyte infiltration level, and low tumor mutation burden (TMB). The combination of ICIs and other treatment schemes for pMMR/MSS CRC patients may achieve a certain effect due to the change in tumor microenvironment (By Figdraw).