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

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.

Targeted Chinese Medicine Delivery by A New Family of Biodegradable Pseudo-Protein Nanoparticles for Treating Triple-Negative Breast Cancer: In Vitro and In Vivo Study

“…For the treatment of TNBC, a combination of NP-GA and Th1 cytokine interferon-g (IFN-g) can be administrated to enhance M1 polarization in the TNBC in our future study. IFN-g is a useful adjuvant immunotherapy for many cancers (53). It also inhibits angiogenesis in the tumor (53).…”

“…IFN-g is a useful adjuvant immunotherapy for many cancers (53). It also inhibits angiogenesis in the tumor (53).…”

Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

“…In addition, IFN-γ is important in differentiation of stromal cells and subsequent cessation of NK cell function since NK cells are known to become activated by the stem cells and not by the well-differentiated cells [ 35 , 36 ]. Thus, IFN-γ can regulate its own production negatively and limit the levels of inflammation [ 35 , 36 , 37 , 38 ].…”

A Palette of Cytokines to Measure Anti-Tumor Efficacy of T Cell-Based Therapeutics

“…IFN-γ has long been studied as the ultimate pro-inflammatory cytokine, with the responsibility to regulate anti-inflammatory responses. It also inhibits differentiation of immunosuppressive regulatory T cells (Tregs), and balances tissue destruction in chronic inflammation conditions [ 5 , 6 ]. Interestingly, depending on the biological context, IFN-γ can enhance or diminish the expression of tumor antigens, thereby determining the extent of anti-tumor immune responses [ 7 ].…”

“…Interestingly, depending on the biological context, IFN-γ can enhance or diminish the expression of tumor antigens, thereby determining the extent of anti-tumor immune responses [ 7 ]. Thus, some pro-tumor consequences of IFN-γ exposure exist, and its role may depend on the length of exposure and absolute abundance of the cytokine within the TME [ 5 ]. Additionally, while necessary, this cytokine does not seem to be sufficient on its own to halt the development of tumors [ 6 ].…”