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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2021

Open Access 01-12-2021 | Review

Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes

Authors: Wantao Wu, Yihan Liu, Shan Zeng, Ying Han, Hong Shen

Published in: Journal of Hematology & Oncology | Issue 1/2021

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Abstract

In this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis.
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Metadata
Title
Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes
Authors
Wantao Wu
Yihan Liu
Shan Zeng
Ying Han
Hong Shen
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2021
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-021-01166-3

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