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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2019

Open Access 01-12-2019 | NSCLC | Review

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

Authors: Pengfei Zhao, Li Li, Xiaoyue Jiang, Qin Li

Published in: Journal of Hematology & Oncology | Issue 1/2019

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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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Metadata
Title
Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy
Authors
Pengfei Zhao
Li Li
Xiaoyue Jiang
Qin Li
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-019-0738-1

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Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice

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Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial

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Fludarabine-treosulfan compared to thiotepa-busulfan-fludarabine or FLAMSA as conditioning regimen for patients with primary refractory or relapsed acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Review

Emerging agents and regimens for hepatocellular carcinoma

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Burden of lymphoma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
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