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

Biomarker Research

Dragica Jorgovanovic¹  Yi Zhang²  Liping Wang³  Mengjia Song⁴ 

[1] Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, 450052, Zhengzhou, Henan, China;State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, China;Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, 450052, Zhengzhou, Henan, China;State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, 450052, Zhengzhou, China;Cancer Center, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, 450052, Zhengzhou, Henan, China;Henan Key Laboratory for Tumor Immunology and Biotherapy, 450052, Zhengzhou, China;Cancer Center, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, 450052, Zhengzhou, Henan, China;Department of Biotherapy, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, 510060, Guangzhou, China;

关键词: IFN-γ;    Cancer;    Tumor microenvironment;    Immunoregulation;    Immunotherapy;    Tumor regression;    Tumor progression;   

DOI  :  10.1186/s40364-020-00228-x

来源: Springer

【 摘 要 】

BackgroundInterferon-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 bodySome 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.ConclusionSignificant 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.

【 授权许可】

CC BY