Int J Biol Sci 2022; 18(7):2821-2832. doi:10.7150/ijbs.71714 This issue

Review

The role of DNA mismatch repair in immunotherapy of human cancer

Yuchen He1,2*, Luyuan Zhang3*, Ruoyu Zhou2*, Yumin Wang4,5✉, Hao Chen1✉

1. Department of General Surgery, The First Affiliated Hospital of USTC; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
2. Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
3. Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
4. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
5. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
*These authors contributed equally to this work.

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Citation:
He Y, Zhang L, Zhou R, Wang Y, Chen H. The role of DNA mismatch repair in immunotherapy of human cancer. Int J Biol Sci 2022; 18(7):2821-2832. doi:10.7150/ijbs.71714. Available from https://www.ijbs.com/v18p2821.htm

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Abstract

Graphic abstract

DNA mismatch repair (MMR) is an important pathway which helps to maintain genomic stability. Mutations in DNA MMR genes are found to promote cancer initiation and foster tumor progression. Deficiency or inactivation of MMR results in microsatellite instability (MSI) which triggers neoantigen generation and impairs tumor growth. Immunotherapies targeting MMR can increase the burden of neoantigens in tumor cells. While MSI has been regarded as an important predictor of sensitivity and drug resistance for immunotherapy-based strategies. Different approaches targeting genomic instability have been demonstrated to be promising in malignancies derived from different tissues. Underlying MMR deficiency-associated immunogenicity is important for improving the therapeutic efficacy of immunotherapies. In this review we provide an overview of the MMR systems, their role in tumorigenesis, drug resistance, prognostic significance and potential targets for therapeutic treatment in human cancers, especially in hematological malignancies.

Keywords: MMR, Development, Immunotherapy, DNA repair, Cancer