Biology, Saint Louis University, Saint Louis, Missouri, USA.
Biology, Saint Louis University, Saint Louis, Missouri, USA
J Immunother Cancer. 2021 Oct;9(10). doi: 10.1136/jitc-2021-003217.
Immunotherapeutic drugs including immune checkpoint blockade antibodies have been approved to treat patients in many types of cancers. However, some patients have little or no reaction to the immunotherapy drugs. The mechanisms underlying resistance to tumor immunotherapy are complicated and involve multiple aspects, including tumor-intrinsic factors, formation of immunosuppressive microenvironment, and alteration of tumor and stromal cell metabolism in the tumor microenvironment. T cell is critical and participates in every aspect of antitumor response, and T cell dysfunction is a severe barrier for effective immunotherapy for cancer. Emerging evidence indicates that extracellular vesicles (EVs) secreted by tumor is one of the major factors that can induce T cell dysfunction. Tumor-derived EVs are widely distributed in serum, tissues, and the tumor microenvironment of patients with cancer, which serve as important communication vehicles for cancer cells. In addition, tumor-derived EVs can carry a variety of immune suppressive signals driving T cell dysfunction for tumor immunity. In this review, we explore the potential mechanisms employed by tumor-derived EVs to control T cell development and effector function within the tumor microenvironment. Especially, we focus on current understanding of how tumor-derived EVs molecularly and metabolically reprogram T cell fates and functions for tumor immunity. In addition, we discuss potential translations of targeting tumor-derived EVs to reconstitute suppressive tumor microenvironment or to develop antigen-based vaccines and drug delivery systems for cancer immunotherapy.
免疫治疗药物,包括免疫检查点阻断抗体,已被批准用于治疗多种癌症患者。然而,一些患者对免疫治疗药物反应很小或没有反应。肿瘤免疫治疗耐药的机制很复杂,涉及多个方面,包括肿瘤内在因素、免疫抑制微环境的形成以及肿瘤微环境中肿瘤和基质细胞代谢的改变。T 细胞是关键的,参与抗肿瘤反应的各个方面,而 T 细胞功能障碍是癌症有效免疫治疗的严重障碍。新出现的证据表明,肿瘤分泌的细胞外囊泡(EVs)是诱导 T 细胞功能障碍的主要因素之一。肿瘤衍生的 EVs 广泛分布在癌症患者的血清、组织和肿瘤微环境中,是癌细胞之间重要的通讯载体。此外,肿瘤衍生的 EVs 可以携带多种免疫抑制信号,驱动 T 细胞功能障碍,从而抑制肿瘤免疫。在这篇综述中,我们探讨了肿瘤衍生的 EVs 控制肿瘤微环境中 T 细胞发育和效应功能的潜在机制。特别是,我们重点介绍了目前对肿瘤衍生的 EVs 如何在分子和代谢水平上重新编程 T 细胞命运和功能以促进肿瘤免疫的理解。此外,我们还讨论了靶向肿瘤衍生 EVs 以重建抑制性肿瘤微环境或开发基于抗原的疫苗和药物递送系统进行癌症免疫治疗的潜在转化。
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