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Review
. 2017 Feb 1;24(1):10.
doi: 10.1186/s12929-017-0317-0.

Escape from IFN-γ-dependent immunosurveillance in tumorigenesis

Chiou-Feng Lin  1   2 , Chih-Ming Lin  3 , Kang-Yun Lee  4   5 , Szu-Yuan Wu  5   6   7   8 , Po-Hao Feng  4   5 , Kuan-Yuan Chen  4   5   9 , Hsiao-Chi Chuang  10 , Chia-Ling Chen  11 , Yu-Chih Wang  12 , Po-Chun Tseng  12 , Tsung-Ting Tsai  12
Affiliations
Review

Escape from IFN-γ-dependent immunosurveillance in tumorigenesis

Chiou-Feng Lin et al. J Biomed Sci. .

Abstract

Immune interferon (IFN), also known as IFN-γ, promotes not only immunomodulation but also antimicrobial and anticancer activity. After IFN-γ binds to the complex of IFN-γ receptor (IFNGR) 1-IFNGR2 and subsequently activates its downstream signaling pathways, IFN-γ immediately causes transcriptional stimulation of a variety of genes that are principally involved in its biological activities. Regarding IFN-γ-dependent immunosurveillance, IFN-γ can directly suppress tumorigenesis and infection and/or can modulate the immunological status in both cancer cells and infected cells. Regarding the anticancer effects of IFN-γ, cancer cells develop strategies to escape from IFN-γ-dependent cancer immunosurveillance. Immune evasion, including the recruitment of immunosuppressive cells, secretion of immunosuppressive factors, and suppression of cytotoxic T lymphocyte responses, is speculated to be elicited by the oncogenic microenvironment. All of these events effectively downregulate IFN-γ-expressing cells and IFN-γ production. In addition to these extrinsic pathways, cancer cells may develop cellular tolerance that manifests as hyporesponsiveness to IFN-γ stimulation. This review discusses the potential escape mechanisms from IFN-γ-dependent immunosurveillance in tumorigenesis.

Keywords: Cancer; Escape; Hyporesponsiveness; IFN-γ; Immunosurveillance.

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Figures

Fig. 1
Fig. 1
Immune surveillance and escape from IFN-γ-dependent anticancer activity. CCL: CC chemokine ligands; CXCL: CXC chemokine ligands; CTL: cytotoxic T lymphocytes; CTLA: cytotoxic T-lymphocyte-associated protein; IDO: indoleamine-pyrrole 2,3-dioxygenase; IFN: interferon; IFNGR: IFN-γ receptors; IL: interleukin; IRF: IFN-regulating factors; JAK: Janus kinase; MDSC: myeloid-derived suppressor cell; MHC: major histocompatibility complex; NK: natural killer; PD-L1: programmed death ligand 1; PGE: prostaglandin E; SHP: src homology-2 containing phosphatase; SOCS: suppressors of cytokine signaling; STAT: signal transducer and activator of transcription; TAM: tumor-associated macrophage; TAP: transporter associated with antigen processing; TGF: transforming growth factor; TNF: tumor necrosis factor; TRAIL: TNF-related apoptosis-inducing ligand; Treg: regulatory T cell
See this image and copyright information in PMC

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