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:Immune cell-derived small extracellular vesicles in cancer treatment.
Immune cell-derived small extracellular vesicles in cancer treatment.
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多数细胞分泌的小型细胞外囊泡(sEV)携带蛋白质、脂质和核酸等生物活性大分子,参与细胞间通讯。部分免疫细胞来源的sEV具有抗癌作用,因此受到关注,有望开发为新型抗癌免疫治疗药物。本文综述了免疫细胞来源sEV在癌症治疗中的生物学作用及最新进展。树突状细胞(DC)、T细胞、自然杀伤(NK)细胞和巨噬细胞来源的sEV,均是基于sEV的癌症治疗候选物。除可作为癌症疫苗外,DC释放的sEV还能激活细胞毒性淋巴细胞并杀伤肿瘤细胞;从NK细胞和嵌合抗原受体(CAR)T细胞中分离的sEV也对癌细胞具有细胞毒性。CD8+ T细胞来源的sEV可抑制肿瘤微环境(TME)中的癌症相关细胞,而CD4+ T细胞来源的sEV可激活B细胞。M1型巨噬细胞来源的sEV能够促使M2型巨噬细胞向M1型重新极化,并形成促炎环境。
因此,未来可考虑单独或联合使用这些sEV治疗癌症患者。此外,对细胞因子刺激后的免疫细胞来源sEV进行工程化改造,也可能增强其抗肿瘤效力。
Small extracellular vesicles (sEVs) secreted by most cells carry bioactive macromolecules including proteins, lipids, and nucleic acids for intercellular communication. Given that some immune cell-derived sEVs exhibit anti-cancer properties, these sEVs have received scientific attention for the development of novel anticancer immunotherapeutic agents. In this paper, we reviewed the latest advances concerning the biological roles of immune cell-derived sEVs for cancer therapy. sEVs derived from immune cells including dendritic cells (DCs), T cells, natural-killer (NK) cells, and macrophages are good candidates for sEV-based cancer therapy.
Besides their role of cancer vaccines, DC-shed sEVs activated cytotoxic lymphocytes and killed tumor cells. sEVs isolated from NK cells and chimeric antigen receptor (CAR) T cells exhibited cytotoxicity against cancer cells. sEVs derived from CD8+ T and CD4+ T cells inhibited cancer-associated cells in tumor microenvironment (TME) and activated B cells, respectively.
M1-macrophage-derived sEVs induced M2 to M1 repolarization and also created a pro-inflammatory environment. Hence, these sEVs, via mono or combination therapy, could be considered in the treatment of cancer patients in the future.
In addition, sEVs derived from cytokine-stimulated immune cells or sEV engineering could improve their anti-tumor potency. [BMB Reports 2022; 55(1): 48-56].
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