肿瘤来源的外泌体与器官驻留细胞结合，在局部免疫微环境重塑过程中激活 S100 分子。然而，关于器官驻留细胞 S100A10 如何介导癌症转移进展，人们知之甚少。在这里，我们提供了S100A10在调节肺部免疫微环境和癌症转移中发挥重要作用的证据。 S100A10 缺陷小鼠减少了肺部癌症转移。此外，通过肿瘤源性外泌体激活肺成纤维细胞内的 S100A10 增加了 CXCL1 和 CXCL8 趋化因子的表达，同时伴随着骨髓源性抑制细胞 (MDSC) 的招募。 S100A10抑制剂如1-取代-4-芳酰基-3-羟基-5-苯基-1 H-5-吡咯-2(5 H)-酮在体内抑制肺转移。我们的研究结果强调了 S100A10 在驱动 MDSC 募集以重塑肺部免疫微环境并提供潜在治疗靶点以阻止癌症肺部转移方面的关键作用。© 2024 作者。经泰勒许可出版

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.