IFN-γ orchestrates tumor elimination, tumor dormancy, tumor escape, and progression

Abstract

Tumor immunoediting consisting of three phases of elimination, equilibrium or dormancy, and escape has been supported by preclinical and clinical data. A comprehensive understanding of the molecular mechanisms by which antitumor immune responses regulate these three phases are important for developing highly tailored immunotherapeutics that can control cancer. To this end, IFN-γ produced by Th1 cells, cytotoxic T cells, NK cells, and NKT cells is a pleiotropic cytokine that is involved in all three phases of tumor immunoediting, as well as during inflammation-mediated tumorigenesis processes. This essay presents a review of literature and suggests that overcoming tumor escape is feasible by driving tumor cells into a state of quiescent but not indolent dormancy in order for IFN-γ-producing tumor-specific T cells to prevent tumor relapse.

Keywords: IFN-γ; immunotherapy; tumor dormancy; tumor immunoediting.

Figure 1.. Multifaceted role of IFN-γ in cancer.

Pro-tumor function of IFN-γ is mediated by chronic inflammation involving inflammatory monocytes and macrophages. Anti-tumor function of IFN-γ is mediated by cells of the adaptive immune system (CTL and Th1), NK cells and NKT cells. The outcome of anti-tumor immune responses is determined by the status of the expression of IFN-γ Rα on target cells such that high levels of IFN-γ Rα render the tumor susceptible to apoptosis while low levels of IFN-γ Rα could result in tumor immunoediting and relapse or maintenance of immunogenic tumor dormancy depending on the type of tumor dormancy being Ki67^- quiescent or Ki67^low indolent, respectively.