Although immunotherapy has been at the forefront of cancer therapy for the last several years, better clinical responses are still desired. Interleukin-33 is perhaps one of the most overlooked antitumor cytokines. Its ability to promote type 1 immune responses, which control tumor growth in preclinical animal models is overshadowed by its association with type 2 immunity and poor prognosis in some human cancers. Accumulating evidence shows that IL-33 is a powerful new tool for restoring and enhancing the body's natural antitumor immunity cycle. Furthermore, the antitumor mechanisms of IL-33 are two-fold, as it can directly boost CD8+ T cell function and restore dendritic cell dysfunction in vivo. Mechanistic studies have identified a novel pathway induced by IL-33 and its receptor ST2 in which dendritic cells avoid dysfunction and retain cross-priming abilities in tumor-bearing conditions. Here, we also comment on IL-33 data in human cancers and explore the idea that endogenous IL-33 may not deserve its reputation for promoting tumor growth. In fact, tumors may hijack the IL-33/ST2 axis to avoid immune surveillance and escape antitumor immunity.

中文翻译：

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IL-33 在肿瘤免疫中的作用：不容小觑。


尽管过去几年免疫疗法一直处于癌症治疗的最前沿，但仍然需要更好的临床反应。 Interleukin-33 可能是最被忽视的抗肿瘤细胞因子之一。它促进 1 型免疫反应（在临床前动物模型中控制肿瘤生长）的能力因其与 2 型免疫和某些人类癌症不良预后的相关性而黯然失色。越来越多的证据表明，IL-33是恢复和增强人体自然抗肿瘤免疫循环的强大新工具。此外，IL-33的抗肿瘤机制是双重的，因为它可以直接增强CD8+T细胞功能并恢复体内树突状细胞功能障碍。机制研究发现了一种由 IL-33 及其受体 ST2 诱导的新途径，其中树突状细胞避免功能障碍并在荷瘤条件下保留交叉启动能力。在这里，我们还评论了人类癌症中的 IL-33 数据，并探讨了内源性 IL-33 可能不值得其促进肿瘤生长的声誉的观点。事实上，肿瘤可能会劫持IL-33/ST2轴来逃避免疫监视并逃避抗肿瘤免疫。