Cited by 1,234Cancer Immunotherapy and BiomarkersImmune cells in cancerinterferon and immune responses

Roles of IFN-γ in tumor progression and regression: A review

Open access
Jorgovanovic, Dragica, Song, Mengjia, Wang, Liping, Zhang, Yi·2020·Biomarker Research

Abstract

BACKGROUND: Interferon-γ (IFN-γ) plays a key role in activation of cellular immunity and subsequently, stimulation of antitumor immune-response. Based on its cytostatic, pro-apoptotic and antiproliferative functions, IFN-γ is considered potentially useful for adjuvant immunotherapy for different types of cancer. Moreover, it IFN-γ may inhibit angiogenesis in tumor tissue, induce regulatory T-cell apoptosis, and/or stimulate the activity of M1 proinflammatory macrophages to overcome tumor progression. However, the current understanding of the roles of IFN-γ in the tumor microenvironment (TME) may be misleading in terms of its clinical application. MAIN BODY: Some researchers believe it has anti-tumorigenic properties, while others suggest that it contributes to tumor growth and progression. In our recent work, we have shown that concentration of IFN-γ in the TME determines its function. Further, it was reported that tumors treated with low-dose IFN-γ acquired metastatic properties while those infused with high dose led to tumor regression. Pro-tumorigenic role may be described through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, upregulation of indoleamine 2,3-dioxygenase, and checkpoint inhibitors such as programmed cell death ligand 1. CONCLUSION: Significant research efforts are required to decipher IFN-γ-dependent pro- and anti-tumorigenic effects. This review discusses the current knowledge concerning the roles of IFN-γ in the TME as a part of the complex immune response to cancer and highlights the importance of identifying IFN-γ responsive patients to improve their sensitivity to immuno-therapies.

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  • The IFN-γ signature, which includes CXCL10, CXCL9, HLA-DRA, IDO1, STAT1, and IFNG, is significant in predicting responses to ICIs therapy.

    “Given this information, the IFN-γ signature, which includes CXCL10, CXCL9, HLA-DRA, IDO1, STAT1, and IFNG, is significant in predicting responses to ICIs therapy [131].”

    From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [131]

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Authors
Jorgovanovic, D., Song, M., Wang, L., & Zhang, Y.
Affiliations
  • Sun Yat-sen University (CN)
  • First Affiliated Hospital of Zhengzhou University (CN)
  • Zhengzhou University (CN)
Corresponding author
  • Wang, Liping
  • Zhang, Yi
Venue
Biomarker Research
Published
2020-09-29
Volume
8
Issue
1
Pages
49-49
ISSN
2050-7771 (ISSN-L)
OpenAlex
W3090386083
Cited by
1,234
References
186
Citations by year
2026: 157 · 2025: 307 · 2024: 294 · 2023: 229 · 2022: 179 · 2021: 65 · 2019: 1 · 2013: 1
FWCI
12.70
Type
journal article
Language
en
Open access
Locations
  • Biomarker Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Key Technologies Research and Development Program (2018YFC1313400, 2016YFC1303501)
  • National Natural Science Foundation of China (81872410, 91942314)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
interferon-gamma, tumor progression, tumor regression, tumor microenvironment, antitumor immunity, immunotherapy, angiogenesis inhibition, regulatory T cells, M1 macrophages, indoleamine 2,3-dioxygenase, PD-L1, MHC downregulation, metastasis, immunotherapy response prediction

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