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IL33 and Mast Cells-The Key Regulators of Immune Responses in Gastrointestinal Cancers?
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-05-29 , DOI: 10.3389/fimmu.2020.01389
Moritz F Eissmann 1 , Michael Buchert 1 , Matthias Ernst 1
Affiliation  

The Interleukin (IL-)1 family IL33 is best known for eliciting type 2 immune responses by stimulating mast cells (MCs), regulatory T-cells (Tregs), innate lymphoid cells (ILCs) and other immune cells. MCs and IL33 provide critical control of immunological and epithelial homeostasis in the gastrointestinal (GI) tract. Meanwhile, the role of MCs in solid malignancies appears tissue-specific with both pro and anti-tumorigenic activities. Likewise, IL33 signaling significantly shapes immune responses in the tumor microenvironment, but these effects remain often dichotomous when assessed in experimental models of cancer. Thus, the balance between tumor suppressing and tumor promoting activities of IL33 are highly context dependent, and most likely dictated by the mixture of cell types responding to IL33. Adding to this complexity is the promiscuous nature by which MCs respond to cytokines other than IL33 and release chemotactic factors that recruit immune cells into the tumor microenvironment. In this review, we integrate the outcomes of recent studies on the role of MCs and IL33 in cancer with our own observations in the GI tract. We propose a working model where the most abundant IL33 responsive immune cell type is likely to dictate an overall tumor-supporting or tumor suppressing outcome in vivo. We discuss how these opposing responses affect the therapeutic potential of targeting MC and IL33, and highlight the caveats and challenges facing our ability to effectively harness MCs and IL33 biology for anti-cancer immunotherapy.



中文翻译:

IL33和肥大细胞-胃肠道肿瘤免疫反应的关键调节因子?

白介素(IL-)1家族IL33以刺激肥大细胞(MC),调节性T细胞(Tregs),先天淋巴样细胞(ILC)和其他免疫细胞引起2型免疫应答而闻名。MC和IL33提供了胃肠道(GI)免疫和上皮稳态的关键控制。同时,MCs在实体恶性肿瘤中的作用似乎具有组织特异性,具有促癌和抗肿瘤活性。同样,IL33信号显着影响肿瘤微环境中的免疫反应,但在癌症实验模型中评估时,这些作用通常仍然是二分的。因此,IL33的肿瘤抑制和肿瘤促进活性之间的平衡高度依赖于上下文,并且最可能由响应IL33的细胞类型的混合物所决定。MC不仅会对IL33产生反应,还会释放趋化因子,从而将免疫细胞募集到肿瘤微环境中,从而使MC产生混杂特性,从而增加了这种复杂性。在这篇综述中,我们将关于MC和IL33在癌症中的作用的最新研究结果与我们在胃肠道中的观察结果进行了整合。我们提出了一种工作模型,其中最丰富的IL33反应性免疫细胞类型可能决定总体的肿瘤支持或肿瘤抑制结果体内。我们讨论了这些相反的反应如何影响靶向MC和IL33的治疗潜力,并突出了我们有效利用MC和IL33生物学进行抗癌免疫治疗的能力所面临的警告和挑战。

更新日期:2020-07-03
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