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Cited by 682Cancer Immunotherapy and BiomarkersGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy

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Zhao, Pengfei, Li, Li, Jiang, Xiaoyue, Li, Qin·2019·Journal of Hematology & Oncology
DOI 10.1186/s13045-019-0738-1PMC PMC6544911
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Abstract

Immunotherapies have led to substantial changes in cancer treatment and have been a persistently popular topic in cancer research because they tremendously improve the efficacy of treatment and survival of individuals with various cancer types. However, only a small proportion of patients are sensitive to immunotherapy, and specific biomarkers are urgently needed to separate responders from nonresponders. Mismatch repair pathways play a vital role in identifying and repairing mismatched bases during DNA replication and genetic recombination in normal and cancer cells. Defects in DNA mismatch repair proteins and subsequent microsatellite instability-high lead to the accumulation of mutation loads in cancer-related genes and the generation of neoantigens, which stimulate the anti-tumor immune response of the host. Mismatch repair deficiency/microsatellite instability-high represents a good prognosis in early colorectal cancer settings without adjuvant treatment and a poor prognosis in patients with metastasis. Several clinical trials have demonstrated that mismatch repair deficiency or microsatellite instability-high is significantly associated with long-term immunotherapy-related responses and better prognosis in colorectal and noncolorectal malignancies treated with immune checkpoint inhibitors. To date, the anti-programmed cell death-1 inhibitor pembrolizumab has been approved for mismatch repair deficiency/microsatellite instability-high refractory or metastatic solid tumors, and nivolumab has been approved for colorectal cancer patients with mismatch repair deficiency/microsatellite instability-high. This is the first time in the history of cancer therapy that the same biomarker has been used to guide immune therapy regardless of tumor type. This review summarizes the features of mismatch repair deficiency/microsatellite instability-high, its relationship with programmed death-ligand 1/programmed cell death-1, and the recent advances in predicting immunotherapy efficacy.

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  • Existing predictive biomarkers (PD-L1 expression, TMB, microsatellite instability, and mismatch repair deficiency) have clinical utility in specific contexts, but their predictive accuracy varies considerably across tumor histologies and patient populations.

    “While these markers have clinical utility in specific contexts, their predictive accuracy varies considerably across tumor histologies and patient populations.”

    From PathTIGR: A pathway topology-informed graph representation learning framework for immunotherapy response prediction (2026) · cites this paper as [17]

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Authors
Zhao, P., Li, L., Jiang, X., & Li, Q.
Affiliations
Capital Medical University (CN)
Corresponding author
Li, Qin
ORCID
Venue
Journal of Hematology & Oncology
Publisher
Springer Science and Business Media LLC
Published
2019-05-31
Volume
12
Issue
1
Pages
54-54
ISSN
1756-8722 (ISSN-L)
DOI
10.1186/s13045-019-0738-1
PMC
PMC6544911
OpenAlex
W2947159010
Cited by
682
References
12
Citations by year
2026: 45 · 2025: 90 · 2024: 100 · 2023: 121 · 2022: 142 · 2021: 111 · 2020: 61 · 2019: 12
FWCI
7.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Hematology & Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
mismatch repair deficiency, microsatellite instability-high, PD-1/PD-L1 inhibitors, immune checkpoint inhibitors, immunotherapy response prediction, predictive biomarkers, pembrolizumab, nivolumab, colorectal cancer, neoantigens, tumor mutational burden, metastatic solid tumors
MeSH terms
Animals, Humans, Immunotherapy, Neoplasms, Prognosis, Treatment Outcome, Microsatellite Instability, DNA Mismatch Repair, B7-H1 Antigen, Programmed Cell Death 1 Receptor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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