期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00847
关键词
type II interferon; immunoregulation; cancer microenvironment; immunotherapy; immune contexture
类别
资金
- Portugal Regional Operational Programme (NORTE) [NORTE-01-0145-FEDER-000012]
- PORTUGAL Partnership Agreement
- European Regional Development Fund (ERDF)
- FCT PhD Programmes by Human Capital Operational Programme (POCH)
- BiotechHealth Programme
- FCT [PD/BD/114013/2015, IF/00638/2014, IF/00004/2014, IF/01066/2012]
- iMM Laco2016 research grant
- [POCI-01-0145-FEDER-016390]
- Fundação para a Ciência e a Tecnologia [PD/BD/114013/2015] Funding Source: FCT
Interferon- gamma (IFN-gamma) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-gamma in tumor immune surveillance, IFN-gamma-based therapies undergoing clinical trials have been of limited success. In fact, recent reports suggested that it may also play a protumorigenic role, namely, through IFN-gamma signaling insensitivity, downregulation of major histocompatibility complexes, and upregulation of indoleamine 2,3-dioxygenase and of checkpoint inhibitors, as programmed cell-death ligand 1. However, the IFN-gamma-mediated responses are still positively associated with patient's survival in several cancers. Consequently, major research efforts are required to understand the immune contexture in which IFN-gamma induces its intricate and highly regulated effects in the tumor microenvironment. This review discusses the current knowledge on the pro- and antitumorigenic effects of IFN-gamma as part of the complex immune response to cancer, highlighting the relevance to identify IFN-gamma responsive patients for the improvement of therapies that exploit associated signaling pathways.
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