Roles of IFN-γ in tumor progression and regression: A review
Open accessAbstract
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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Noriega, L., Díaz, A., Limón, I. D., et al. (2019) · Journal of Molecular Modeling · doi:10.1007/s00894-019-4128-y · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
Combination strategies to maximize the benefits of cancer immunotherapy
Zhu, S., Zhang, T., Zheng, L., Liu, H., Song, W., Liu, D., Li, Z., & Pan, C.-X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01164-5 · Cited by 654 · see citing works
Research progress on interferon and cellular senescence
Wang, D., Chen, K., Wang, Z., Wu, H., & Li, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202400808rr · Cited by 23 · see citing works
Li, P., Dong, Z., Jiang, Q., Yu, C., Liu, Y., Yuan, R., Qiu, Y., Meng, T., Hu, F., & Yuan, H. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114406 · Cited by 6 · see citing works
- 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)
- PMC
- PMC7526126
- 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
- gold
- doi.org
- 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
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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