The next bastion to be conquered in immunotherapy: microsatellite stable colorectal cancer

Front Immunol. 2023 Dec 22:14:1298524. doi: 10.3389/fimmu.2023.1298524. eCollection 2023.

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and its incidence continues to rise, particularly in developing countries. The advent of immune checkpoint inhibitors (ICIs) has represented a significant advancement in CRC treatment. Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) serves as a biomarker for immunotherapy, with dMMR/MSI-H CRC exhibiting significantly better response rates to immunotherapy compared to proficient mismatch repair (pMMR)or microsatellite stable (MSS) CRC. While some progress has been made in the treatment of pMMR/MSS CRC in recent years, it remains a challenging issue in clinical practice. The tumor microenvironment (TME) plays a crucial role not only in the development and progression of CRC but also in determining the response to immunotherapy. Understanding the characteristics of the TME in pMMR/MSS CRC could offer new insights to enhance the efficacy of immunotherapy. In this review, we provide an overview of the current research progress on the TME characteristics and advancements in immunotherapy for pMMR/MSS CRC.

Keywords: colorectal cancer; immune checkpoint inhibitors; immunotherapy; microsatellite stability; tumor microenvironment.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / therapy
  • DNA Mismatch Repair
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy*
  • Microsatellite Instability
  • Microsatellite Repeats / genetics
  • Tumor Microenvironment / genetics

Substances

  • Immune Checkpoint Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82000581), Key Specialty Construction Project of Pudong Health Commission of Shanghai (PWZzk2022-09), and Youth Initial Found of Naval Medicine University (2022DN078).