Immunotherapy in pMMR/MSS Metastatic Colorectal Cancer

Abstract

Over the last two decades, there have been remarkable improvements in the management of patients with colorectal cancer (CRC) characterized by deficient mismatch repair or high microsatellite instability. This progress can be attributed to the emergence of immune checkpoint inhibitors. However, proficient mismatch repair /microsatellite stable (pMMR/ MSS) CRC has not derived this advantage. Unfortunately, it has yet to be demonstrated that immune checkpoint inhibitor therapy yields significant clinical advantages for patients with pMMR/MSS. In these patients, many studies have been conducted on the use of immune checkpoint inhibitors in combination with tyrosine kinase inhibitors and targeted therapies to ascertain their potential for amplifying antitumor efficacy within the tumor microenvironment, enhancing clinical and radiologic outcomes. We also examine the utilization of immune checkpoint inhibitors in CRCs with pMMR/MSS and assess the molecular obstacles that block the efficacy of immunotherapy. In this review, we analyze the use of immune checkpoint inhibitors in treating pMMR/MSS mCRC and the molecular barriers to effective immunotherapy. Additionally, we discuss strategies to enhance the responsiveness of pMMR/MSS CRC to immunotherapy.