Autoimmunity as a double agent in tumor killing and cancer promotion.
Autoimmunity as a double agent in tumor killing and cancer promotion.
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DOI：
10.3389/fimmu.2014.00116
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发表时间：
2014
影响因子：
7.3
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Toomer KH;Chen Z
通过操纵免疫系统的癌症免疫疗法在治疗人类癌症方面具有巨大的潜力。然而，最近针对负性免疫调节剂细胞毒性 T 淋巴细胞抗原 4、程序性死亡 1 (PD-1) 和 PD-1 受体配体 (PD-L1) 的试验表明，具有临床意义的抗肿瘤反应通常与诱导自身免疫毒性有关。这一发现表明，引发自身免疫的相同免疫机制也可能有助于破坏肿瘤。鉴于肿瘤的免疫学特性可能很大程度上是免疫豁免的自身，因此在癌症免疫治疗的背景下，自身免疫可能并不代表完全不良的结果。相反，癌细胞的靶向杀伤和健康组织的自身免疫损伤可能通过分子机制，特别是炎症细胞因子信号传导，错综复杂地联系在一起。另一方面，由于慢性炎症是一种公认的促进肿瘤发展的疾病，因此自身免疫似乎可以成为介导促肿瘤或抗肿瘤作用的“双重作用”。本综述调查了几种重要细胞因子的促肿瘤和杀肿瘤活性：IFN-γ、TNF-α、TGF-β、IL-17、IL-23、IL-4 和 IL-13，由与先天免疫细胞相互作用的 T 辅助细胞的三个主要亚群产生。许多细胞因子在不同的人类和动物模型中对癌症的发展产生不同且看似矛盾的影响，这表明它们的功能具有高度的背景依赖性。我们假设这些炎症细胞因子可以介导自身免疫、抗肿瘤免疫和肿瘤发生的反馈循环。了解自身免疫反应中细胞因子在癌症中的多样化和矛盾的作用，将推进改善癌症免疫治疗的长期目标，同时通过适当的监测和预防措施，最大限度地减少免疫介导的组织损伤的危害和从头肿瘤发生的可能性。
Cancer immunotherapy through manipulation of the immune system holds great potential for the treatment of human cancers. However, recent trials targeting the negative immune regulators cytotoxic T-lymphocyte antigen 4, programed death 1 (PD-1), and PD-1 receptor ligand (PD-L1) demonstrated that clinically significant antitumor responses were often associated with the induction of autoimmune toxicity. This finding suggests that the same immune mechanisms that elicit autoimmunity may also contribute to the destruction of tumors. Given the fact that the immunological identity of tumors might be largely an immunoprivileged self, autoimmunity may not represent a wholly undesirable outcome in the context of cancer immunotherapy. Rather, targeted killing of cancer cells and autoimmune damage to healthy tissues may be intricately linked through molecular mechanisms, in particular inflammatory cytokine signaling. On the other hand, since chronic inflammation is a well-recognized condition that promotes tumor development, it appears that autoimmunity can be a “double agent” in mediating either pro-tumor or antitumor effects. This review surveys the tumor-promoting and tumoricidal activities of several prominent cytokines: IFN-γ, TNF-α, TGF-β, IL-17, IL-23, IL-4, and IL-13, produced by three major subsets of T helper cells that interact with innate immune cells. Many of these cytokines exert divergent and seemingly contradictory effects on cancer development in different human and animal models, suggesting a high degree of context dependence in their functions. We hypothesize that these inflammatory cytokines could mediate a feedback loop of autoimmunity, antitumor immunity, and tumorigenesis. Understanding the diverse and paradoxical roles of cytokines from autoimmune responses in the setting of cancer will advance the long-term goal of improving cancer immunotherapy, while minimizing the hazards of immune-mediated tissue damage and the possibility of de novo tumorigenesis, through proper monitoring and preventive measures.
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影响因子：
64.8
作者：
通讯作者：
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转化生长因子-beta（TGFBETA）信号传导的故事：soigné谜。
影响因子：
4.6
作者：
Chaudhury, Arindam;Howe, Philip H.
通讯作者：
Howe, Philip H.
影响因子：
4.4
作者：
Devarajan, Priyadharshini;Chen, Zhibin
通讯作者：
Chen, Zhibin
DOI：
10.1084/jem.20101876
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
De Monte L;Reni M;Tassi E;Clavenna D;Papa I;Recalde H;Braga M;Di Carlo V;Doglioni C;Protti MP
通讯作者：
Protti MP
影响因子：
11.2
作者：
Connolly EC;Saunier EF;Quigley D;Luu MT;De Sapio A;Hann B;Yingling JM;Akhurst RJ
通讯作者：
Akhurst RJ