美国俄勒冈健康与科学大学Naoki Oshimori研究组近日取得一项新成果。他们发现肿瘤初始细胞（TICs）通过形成IL-33-TGF-β小生境信号回路促进癌症恶化。相关论文发表在2020年7月17日出版的《科学》杂志上。

研究人员使用鳞状细胞癌小鼠模型发现TIC在肿瘤进展初期和耐药性所需微环境的形成过程中起着关键作用。TIC的抗氧化活性是由转录因子NRF2介导，这促进了核细胞因子白介素33（IL-33）的释放。该细胞因子促进高亲和力免疫球蛋白E受体FcεRIα的表达且与促进与TIC相接巨噬细胞的分化。

反过来，这些响应IL-33的FcεRIα⁺巨噬细胞将旁分泌转化生长因子β（TGF-β）信号传递给TIC，诱导肿瘤细胞的侵袭性和耐药性，并进一步上调IL-33的表达。这种由TIC诱导的IL-33–TGF-β前馈环通路可能被用于癌症治疗。

据了解，TICs与小生境微环境之间的交流是潜在的癌症治疗途径。

附：英文原文

Title: Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression

Author: Sachiko Taniguchi, Ajit Elhance, Avery Van Duzer, Sushil Kumar, Justin J. Leitenberger, Naoki Oshimori

Issue&Volume: 2020/07/17

Abstract: Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation of macrophages that express the high-affinity immunoglobulin E receptor FcεRIα and are in close proximity to TICs. In turn, these IL-33–responding FcεRIα+ macrophages send paracrine transforming growth factor β (TGF-β) signals to TICs, inducing invasive and drug-resistant properties and further upregulating IL-33 expression. This TIC-driven, IL-33–TGF-β feedforward loop could potentially be exploited for cancer treatment.

DOI: 10.1126/science.aay1813

Source: https://science.sciencemag.org/content/369/6501/eaay1813