Immunotherapy in pMMR/MSS Pancreatic Cancer

Abstract

Over the last two decades, there have been remarkable improvements in the management of patients with various solid tumors characterized by deficient mismatch repair or high microsatellite instability. This progress can be attributed to the emergence of immune checkpoint inhibitors. However, pancreatic cancer with proficient mismatch repair/microsatellite stable (pMMR/MSS) status 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 pancreatic cancer. 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 pancreatic cancers 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 pancreatic cancer and the molecular barriers to effective immunotherapy. Additionally, we discuss strategies to enhance the responsiveness of pMMR/MSS pancreatic cancer to immunotherapy.