RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exosome-Mediated Immunosuppression in Tumor Microenvironments.
Exosome-Mediated Immunosuppression in Tumor Microenvironments.
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外泌体是几乎所有细胞类型分泌的膜性结构。作为细胞间通讯的关键信使,外泌体将生物活性货物递送至受体细胞,并参与多种病理生理过程,包括免疫调节。我们的开创性研究揭示,癌细胞释放程序性死亡配体1阳性外泌体进入循环,通过T细胞在全身范围内对抗抗肿瘤免疫。肿瘤细胞来源的外泌体(TDEs)也对其他免疫细胞发挥免疫抑制作用,包括树突状细胞(DCs)、巨噬细胞、自然杀伤(NK)细胞和髓源性抑制细胞(MDSCs)。此外,肿瘤微环境(TMEs)中非肿瘤细胞分泌的外泌体也发挥免疫抑制效应。本综述系统总结了肿瘤微环境中外泌体诱导的免疫抑制,其调节肿瘤生长、侵袭、转移和免疫治疗耐药。此外,还讨论了针对外泌体介导肿瘤发展的分子机制的治疗策略,这可能有助于克服肿瘤治疗中的若干障碍,如免疫耐受。深入了解外泌体在抗肿瘤免疫中的具体功能可能有助于创新疗法的开发。
Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to recipient cells and are involved in multiple physiopathological processes, including immunoregulation.
Our pioneering study revealed that cancer cells release programmed death-ligand 1-positive exosomes into the circulation to counter antitumor immunity systemically via T cells. Tumor cell-derived exosomes (TDEs) also play an immunosuppressive role in other immunocytes, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs).
Moreover, exosomes secreted by nontumor cells in the tumor microenvironments (TMEs) also exert immunosuppressive effects. This review systematically provides a summary of the immunosuppression induced by exosomes in tumor microenvironments, which modulates tumor growth, invasion, metastasis, and immunotherapeutic resistance.
Additionally, therapeutic strategies targeting the molecular mechanism of exosome-mediated tumor development, which may help overcome several obstacles, such as immune tolerance in oncotherapy, are also discussed. Detailed knowledge of the specific functions of exosomes in antitumor immunity may contribute to the development of innovative treatments.
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