Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies

Postgrad Med J. 2024 May 18;100(1184):373-381. doi: 10.1093/postmj/qgad136.

Abstract

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.

Keywords: MSS; colorectal cancer; immunotherapy; novel therapeutics; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / therapy
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Microsatellite Instability*
  • Mutation