Interferon γ and Its Important Roles in Promoting and Inhibiting Spontaneous and Therapeutic Cancer Immunity
Interferon γ and Its Important Roles in Promoting and Inhibiting Spontaneous and Therapeutic Cancer Immunity
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DOI：
10.1101/cshperspect.a028480
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发表时间：
2019-03-01
影响因子：
7.2
通讯作者：
Schreiber, Robert D.
中科院分区：
文献类型：
--
作者：
Alspach, Elise;Lussier, Danielle M.;Schreiber, Robert D.
干扰素-γ最初是在细胞对病毒感染的抵抗研究中发现的，现在被认为是干扰素家族中的一个独特的成员，不仅在协调针对病毒、细菌和肿瘤的先天和获得性免疫反应中发挥关键作用，而且在促进病理性炎症过程中也发挥着关键作用。干扰素-γ的产生主要限于T淋巴细胞和自然杀伤(NK)细胞，最终可导致由辅助性T细胞(Th)1、CD4(+)T细胞和CD8(+)细胞溶解T细胞组成的极化免疫反应的产生。相反，在渐进性生长的肿瘤中，干扰素-γ在时间上的不同阐述也促进了一种适应性抵抗状态，这是由于肿瘤细胞靶点上的抑制分子，如肿瘤细胞靶点上的程序性死亡配体1(PD-L1)和肿瘤微环境中额外的宿主细胞上调而引起的。本文综述了干扰素-γ在免疫细胞激活和分化过程中的各种正负作用，以及干扰素-γ在肿瘤微环境中的矛盾作用，这些效应决定了肿瘤患者的最终命运。
Originally identified in studies of cellular resistance to viral infection, interferon (IFN)-gamma is now known to represent a distinct member of the IFN family and plays critical roles not only in orchestrating both innate and adaptive immune responses against viruses, bacteria, and tumors, but also in promoting pathologic inflammatory processes. IFN-gamma production is largely restricted to T lymphocytes and natural killer (NK) cells and can ultimately lead to the generation of a polarized immune response composed of T helper (Th) 1 CD4(+) T cells and CD8(+) cytolytic T cells. In contrast, the temporally distinct elaboration of IFN-gamma in progressively growing tumors also promotes a state of adaptive resistance caused by the up-regulation of inhibitory molecules, such as programmed-death ligand 1 (PD-L1) on tumor cell targets, and additional host cells within the tumor microenvironment. This review focuses on the diverse positive and negative roles of IFN-gamma in immune cell activation and differentiation leading to protective immune responses, as well as the paradoxical effects of IFN-gamma within the tumor microenvironment that determine the ultimate fate of that tumor in a cancer-bearing individual.