肿瘤细胞治疗研究
英文原题：Extracellular vesicle-mediated immunoregulation in cancer.
Extracellular vesicle-mediated immunoregulation in cancer.
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细胞外囊泡（EV）已成为肿瘤进展过程中的免疫调节因子。这些小囊泡包裹多种分子，包括DNA、RNA和蛋白质。EV与受体细胞接触后可传递多种生理特性，例如EV表面蛋白可发挥配体作用。靶向细胞毒性T淋巴细胞相关抗原4（CTLA4）、程序性细胞死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）的免疫检查点阻断已使部分癌症患者获益；EV表面的PD-L1是一种关键免疫调节因子。抑制EV分泌可增强免疫检查点阻断抗体的免疫治疗效果。除免疫检查点阻断外，CAR-T（CAR-T）细胞疗法也已成功用于清除癌细胞。有趣的是，CAR-T 细胞来源的EV表面也表达CAR。与CAR-T 细胞相比，表达CAR的EV不表达PD-1，因此其抗肿瘤作用不会因PD-1而减弱。本综述介绍目前对EV参与癌症免疫的认识，并总结EV在免疫调节中的关键作用。
Extracellular vesicles (EVs) have emerged as immunomodulatory regulators during tumor progression. These small vesicles encapsulate a variety of molecules, including DNA, RNA, and proteins. When EVs come in contact with recipient cells, the EVs transmit various physiological characteristics; for example, proteins on the surface of EVs act as ligands.
Immune checkpoint blockade targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown promise in a subset of cancer patients. PD-L1 on EVs acts as a key immunomodulator. Suppression of EV secretion enhances the efficacy of immunotherapy using immune checkpoint blockade antibodies.
In addition to immune checkpoint blockade therapy, chimeric antigen receptor T (CAR-T) cell therapy has also been used to successfully eliminate cancer cells. Interestingly, CAR-T-cell-derived EVs express CAR on their surface. Compared with CAR-T cells, CAR-expressing EVs do not express PD1, so their antitumor effect cannot be weakened. In this review, we describe the current understanding of EVs in cancer immunity and summarize their crucial roles in immunomodulation.
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