[Research progress on biomarkers for proficient mismatch repair/microsatellite stable colorectal cancer in the immunotherapy era].

Abstract

Immunotherapy based on immune checkpoint inhibitor (ICI) has shown remarkable efficacy in the treatment of microsatellite instability (MSI)-high CRC. However, the monotherapy of ICI in microsatellite stable (MSS) CRC has not been satisfactory. Some patients with MSS CRC can benefit from various combination immunotherapy regimens. Identifying appropriate biomarkers to select MSS-type CRC patients who will benefit from ICI treatment prior to therapy initiation and dynamically monitoring treatment efficacy during the therapeutic course have become crucial components of precision medicine in clinical practice. This article reviews the current research status of traditional biomarkers such as tumor mutation burden (TMB) and PD-L1 expression. It also explores the latest research progress and clinical translation potential of emerging biomarkers, including POLE/POLD1 mutations, immune score, circulating tumor DNA, and gut microbiome. Furthermore, it addresses the challenges in the clinical application of biomarkers, such as the controversy over TMB cutoff values and the heterogeneity of PD-L1 expression. Finally, it outlines future research directions with the aim of providing a basis for clinical decision-making in immunotherapy and facilitating the realization of precision medicine.