Predictive biomarkers of colon cancer immunotherapy: Present and future

Abstract

Immunotherapy has revolutionized colon cancer treatment. Immune checkpoint inhibitors (ICIs) have shown clinical benefits for colon cancer patients, especially those with high microsatellite instability (MSI-H). In 2020, the US Food and Drug Administration (FDA)-approved ICI pembrolizumab as the first-line treatment for metastatic MSI-H colon cancer patients. Additionally, neoadjuvant immunotherapy has presented efficacy in treating early-stage colon cancer patients. Although MSI has been thought of as an effective predictive biomarker for colon cancer immunotherapy, only a small proportion of colon cancer patients were MSI-H, and certain colon cancer patients with MSI-H presented intrinsic or acquired resistance to immunotherapy. Thus, further search for predictive biomarkers to stratify patients is meaningful in colon cancer immunotherapy. Except for MSI, other biomarkers, such as PD-L1 expression level, tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), certain gut microbiota, ctDNA, and circulating immune cells were also proposed to be correlated with patient survival and ICI efficacy in some colon cancer clinical studies. Moreover, developing new diagnostic techniques helps identify accurate predictive biomarkers for colon cancer immunotherapy. In this review, we outline the reported predictive biomarkers in colon cancer immunotherapy and further discuss the prospects of technological changes for biomarker development in colon cancer immunotherapy.

Keywords: biomarker; colon cancer; immune checkpoint inhibitor (ICI); immunotherapy; predictive.

Figure 1

Predictive biomarkers of colon cancer immunotherapy MSI, microsatellite instability; TMB, total mutation burden; POLE:/POLD1, DNA polymerase ϵ (POLE) and δ (POLD1); TILs, tumor-infiltrating lymphocytes; PD-L1, programmed cell death-ligand 1; TLS, tertiary lymphoid structure; CAF, cancer-associated fibroblast; ctDNA, circulating tumor DNA; bTMB, blood total mutation burden; NLR, neutrophil-lymphocyte ratio.