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Updated: Jul 26, 2025

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
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Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

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DNA mismatch repair in cancer immunotherapy

Junhong Guan1, Guo-Min Li2

  • 1Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China.

NAR Cancer
|June 16, 2023
PubMed

Insights

Tumors with defective DNA mismatch repair (dMMR) respond well to immune checkpoint inhibitors (ICIs). This review explores dMMR immunotherapy mechanisms, resistance issues, and strategies to improve treatment effectiveness for MSI tumors.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Defects in DNA mismatch repair (dMMR) lead to microsatellite instability (MSI) in tumors.
  • Patients with dMMR/MSI tumors benefit from immune checkpoint inhibitor (ICI) therapy, specifically targeting PD-1/PDL1 pathways.

Purpose of the Study:

  • To review the discovery, development, and molecular underpinnings of dMMR-mediated immunotherapy.
  • To discuss the mechanisms of ICI response in dMMR tumors and address challenges of therapeutic resistance.

Main Methods:

  • Literature review of studies on dMMR, MSI, and ICI therapy.
  • Analysis of molecular mechanisms driving ICI response and resistance in dMMR tumors.

Main Results:

  • dMMR tumors generate neoantigens, activate the cGAS-STING pathway, exhibit type-I interferon signaling, and recruit tumor-infiltrating lymphocytes, contributing to ICI sensitivity.
  • Approximately 50% of dMMR tumors do not respond to current ICI therapy, indicating significant resistance.

Conclusions:

  • Understanding dMMR-mediated immunotherapy is crucial for optimizing cancer treatment.
  • Further research into overcoming resistance mechanisms is essential to improve clinical outcomes for patients with dMMR tumors receiving ICI therapy.

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