Biomarkers and Immunotherapy for Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the second major cause of mortality from cancer globally. Most CRCs are sporadic and may be classified into three main genetic pathways: the chromosomal instability (CIN) pathway, the microsatellite instability (MSI) pathway and the CpG island methylator phenotype (CIMP) pathway, which are associated with genetic mutations or epigenetic alterations and have the possibility to intersect, thus making the treatment of CRC challenging. Immunotherapy has offered some promising insights by inducing antitumor immune responses, but its effectiveness is restricted to certain groups of CRC patients with specific characteristics. Several biomarkers have demonstrated their potentials to predict the outcomes of immunotherapy in individual patients. Some of them include the extent of tumor mutations (MMR/MSI, POLE/POLD1, KRAS), PDL-1 expression, pre-existing immunity and gut microbial compositions. Immune checkpoint inhibitors (ICIs-)-based immunotherapy is considered to be the relatively traditional immunotherapeutic strategy in the treatment of CRC. However, it mainly targets CRCs with defective mismatch repair (dMMR) mechanisms. The more recently developed immunotherapies include cancer vaccines (molecular-based, cell-based and vector-based vaccines) and adoptive cell therapy (ACT), which have the potential to further enhance the stimulation of antitumor immune responses. This review summarizes the predictive biomarkers that have the potential application in CRC treatment, and discusses the immunotherapeutic strategies targeting CRCs that have been developed or are currently under investigation.