细胞外囊泡 (EV) 在许多生理过程中介导细胞间通讯，并可以调节癌症个体的免疫反应。大多数关于 EV 在癌症中的研究都集中在它们的肿瘤促进特性上。除了携带抗原外，EV 是否以及如何介导肿瘤消退尚未得到很好的表征。使用高免疫原性回归细胞与低免疫原性进展肿瘤细胞的小鼠模型，我们描述了 EV 在激活巨噬细胞和促进肿瘤排斥中的作用。我们发现相对于进展细胞，回归细胞分泌的 EV 中信号分子 MAP2K1 (MEK1) 更丰富。进展型 EV 的 MEK1 水平与回归型 EV 相似，可以通过间接促进同基因和第三方肿瘤的适应性免疫来抑制肿瘤生长。这种效应需要 MEK1 活性，并且可以通过激活巨噬细胞通过细胞因子干扰素-γ 促进针对肿瘤的适应性免疫反应来实现。我们的结果表明，MEK 抑制可能对癌症治疗有害，因为 MEK1 在 EV 中发挥着重要的细胞外在肿瘤抑制作用。此外，通过 EV、纳米颗粒或其他方式将 MEK1 递送至肿瘤相关巨噬细胞，可能是通过激活抗肿瘤免疫来治疗癌症的有用策略。© 2024 作者。 《Journal of Extracellular Vesicles》由 Wiley periodicals LLC 代表国际细胞外囊泡学会出版。

Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon-gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell-extrinsic, tumour-suppressive role within EVs. Moreover, the delivery of MEK1 to tumour-associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti-tumour immunity.© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.