Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion.
Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion.
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DOI：
10.3389/fimmu.2018.00847
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发表时间：
2018
影响因子：
7.3
通讯作者：
Oliveira MJ
中科院分区：
文献类型：
--
作者：
Castro F;Cardoso AP;Gonçalves RM;Serre K;Oliveira MJ
干扰素-γ (IFN-γ)是一种具有抗增殖、促凋亡和抗肿瘤机制的多效分子。这种效应细胞因子通常被认为是免疫的主要效应因子，尽管有不利影响，但已用于治疗几种疾病。尽管广泛的证据表明IFN-γ在肿瘤免疫监视中，但临床试验中基于IFN-γ的治疗方法取得的成功有限。事实上，最近的报道表明，它也可能通过IFN-γ信号不敏感、主要组织相容性复合物下调、吲哚胺2,3-双加氧酶和检查点抑制剂上调（作为程序性细胞死亡配体1）发挥致瘤作用。然而，在一些癌症中，IFN-γ介导的反应仍然与患者的生存呈正相关。因此，需要进行大量的研究工作来了解IFN-γ在肿瘤微环境中诱导其复杂且高度调控的免疫环境。这篇综述讨论了IFN-γ作为癌症复杂免疫应答的一部分的促肿瘤和抗肿瘤作用的现有知识，强调了识别IFN-γ应答患者对利用相关信号通路的治疗方法的改进的相关性。
Interferon-gamma (IFN-γ) 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-γ in tumor immune surveillance, IFN-γ-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-γ 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-γ-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-γ 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-γ as part of the complex immune response to cancer, highlighting the relevance to identify IFN-γ responsive patients for the improvement of therapies that exploit associated signaling pathways.