The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape.
The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape.
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DOI：
10.3390/cancers13133281
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发表时间：
2021-06-30
期刊：
影响因子：
5.2
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Choi MR;Sosman JA;Zhang B
白细胞介素 33 (IL-33) 通常从受损细胞中释放出来，充当危险信号。 IL-33 通过与其在大多数免疫细胞上持续表达的致瘤性 2 (ST2) 受体抑制相互作用来发挥其功能。因此，IL-33/ST2信号传导可以调节免疫反应，积极参与多种病理状况，例如癌症。就像面朝相反方向的双面剑一样，IL-33/ST2 信号传导可能通过免疫和非免疫细胞成分对癌症进展发挥矛盾的作用。越来越多的证据表明，IL-33 具有促肿瘤和抗肿瘤特性，具体取决于不同肿瘤免疫微环境的复杂性质。我们总结并讨论了IL-33对癌症进展和治疗的矛盾作用的最新研究，旨在更好地了解IL-33作为治疗靶点的各种方式。白介素 33 (IL-33) 是 IL-1 细胞因子家族的成员，通过促进 1 型和 2 型免疫反应，在维持组织稳态以及过敏、传染病和癌症等病理状况方面发挥着关键作用。通过其特异性受体 ST2，IL-33 通过激活多种细胞内信号通路发挥多方面的功能。 ST2 在不同类型的免疫细胞中表达，包括 Th2 细胞、Th1 细胞、CD8+ T 细胞、调节性 T 细胞 (Treg)、细胞毒性 NK 细胞、第 2 类先天淋巴细胞 (ILC2) 和骨髓细胞。在癌症发生和进展过程中，肿瘤微环境 (TME) 中 IL-33/ST2 轴的异常调节通过调节先天性和适应性免疫细胞成分从外在和内在介导免疫编辑。本综述的总结结果表明，IL-33 具有双重功能，即促肿瘤发生和抗肿瘤发生作用，具体取决于肿瘤类型、表达水平、细胞背景和细胞因子环境。更好地了解 IL-33 在上皮细胞、基质细胞和免疫细胞区室中的独特作用将有利于癌症免疫治疗中 IL-33/ST2 轴靶向策略的开发。
Interleukin-33 (IL-33) is often released from damaged cells, acting as a danger signal. IL-33 exerts its function by interacting with its receptor suppression of tumorigenicity 2 (ST2) that is constitutively expressed on most immune cells. Therefore, IL-33/ST2 signaling can modulate immune responses to participate actively in a variety of pathological conditions, such as cancer. Like a two-faced Janus, which faces opposite directions, IL-33/ST2 signaling may play contradictory roles on its impact on cancer progression through both immune and nonimmune cellular components. Accumulating evidence demonstrates both pro- and anti-tumorigenic properties of IL-33, depending on the complex nature of different tumor immune microenvironments. We summarize and discuss the most recent studies on the contradictory effects of IL-33 on cancer progression and treatment, with a goal to better understanding the various ways for IL-33 as a therapeutic target. Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multifaceted functions through the activation of diverse intracellular signaling pathways. ST2 is expressed in different types of immune cells, including Th2 cells, Th1 cells, CD8+ T cells, regulatory T cells (Treg), cytotoxic NK cells, group 2 innate lymphoid cells (ILC2s), and myeloid cells. During cancer initiation and progression, the aberrant regulation of the IL-33/ST2 axis in the tumor microenvironment (TME) extrinsically and intrinsically mediates immune editing via modulation of both innate and adaptive immune cell components. The summarized results in this review suggest that IL-33 exerts dual-functioning, pro- as well as anti-tumorigenic effects depending on the tumor type, expression levels, cellular context, and cytokine milieu. A better understanding of the distinct roles of IL-33 in epithelial, stromal, and immune cell compartments will benefit the development of a targeting strategy for this IL-33/ST2 axis for cancer immunotherapy.
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影响因子：
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作者：
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