胰腺癌的特点是具有促进癌症进展的免疫抑制肿瘤微环境（TME）。 TME 的组装涉及许多影响因素。迁移体最近被鉴定为迁移细胞中的细胞器，在细胞间信号传导中发挥着关键作用。然而，对其与癌症的关系的研究仍处于起步阶段。迄今为止，胰腺癌细胞是否产生迁移体及其在 TME 形成中的潜在作用仍有待探索。在这项研究中，发现小鼠和人类胰腺癌细胞确实可以产生迁移体，称为胰腺癌细胞衍生的迁移体（PCDM），它能积极促进癌症进展。此外，利用趋化因子抗体阵列和定量质谱分析，我们观察到 PCDM 中存在的趋化因子、细胞因子和蛋白质与其原始细胞体相比存在显着差异。值得注意的是，PCDM 表现出丰富的免疫抑制诱导因子。此外，巨噬细胞可以直接摄取PCDM，导致M2样标记物高水平表达并分泌促癌因子。 PCDM 诱导的巨噬细胞在部分通过 ARG-1 抑制 T 细胞增殖和活化方面发挥着关键作用。总之，这项研究提供了令人信服的证据，证明胰腺癌细胞会产生迁移体，迁移体通过促进免疫抑制性 TME 在促进肿瘤进展中发挥着至关重要的作用。将迁移体作为治疗靶点的探索可能为胰腺癌定制免疫疗法的开发铺平道路。版权所有 © 2024。由 Elsevier B.V. 出版。

Pancreatic cancer is distinguished by an immunosuppressive tumor microenvironment (TME) that facilitates cancer progression. The assembly of the TME involves numerous contributing factors. Migrasomes, recently identified as cellular organelles in migrating cells, play a pivotal role in intercellular signaling. However, research into their involvement in cancers remains nascent. Thus far, whether pancreatic cancer cells generate migrasomes and their potential role in TME formation remains unexplored. In this study, it was found that both murine and human pancreatic cancer cells could indeed generate migrasomes, termed pancreatic cancer cell-derived migrasomes (PCDMs), which actively promote cancer progression. Moreover, utilizing chemokine antibody arrays and quantitative mass spectrometry analysis, we observed significant differences between the chemokines, cytokines, and proteins present in PCDMs compared to their originating cell bodies. Notably, PCDMs exhibited an enrichment of immunosuppression-inducing factors. Furthermore, macrophages could directly uptake PCDMs, leading to the expression of high levels of M2-like markers and secretion of tumor-promoting factors. PCDM-induced macrophages played a pivotal role in inhibiting T cell proliferation and activation partially through ARG-1. In summary, this study provides compelling evidence that pancreatic cancer cells generate migrasomes, which play a crucial role in promoting tumor progression by contributing to an immunosuppressive TME. The exploration of migrasomes as a therapeutic target could pave the way for the development of tailored immunotherapies for pancreatic cancer.Copyright © 2024. Published by Elsevier B.V.