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:Tumor-educated cells in tumor microenvironment: Key drivers of immunotherapy resistance.
Tumor-educated cells in tumor microenvironment: Key drivers of immunotherapy resistance.
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在过去十年中,针对细胞毒性T淋巴细胞抗原-4(CTLA-4)、程序性细胞死亡1(PD-1)和PD-1配体(PD-L1)的免疫疗法已被批准用于实体瘤。
然而,部分患者因耐药而表现出次优的临床结局。肿瘤微环境(TME)通过介导肿瘤细胞与非肿瘤细胞(包括树突状细胞、T细胞、B细胞、巨噬细胞、中性粒细胞、NK细胞和髓源性抑制细胞(MDSC))之间的相互作用,显著影响免疫治疗的效率。这些非肿瘤细胞常表现出两种功能改变的表型,而肿瘤细胞通过肿瘤教育驱动其向促肿瘤方向转变。肿瘤教育细胞(TEC)是受肿瘤细胞影响的细胞,其获得免疫抑制表型并通过对抗癌治疗产生耐药性促进肿瘤进展。这些细胞响应肿瘤信号发生修饰,从而影响其在肿瘤进展中的作用。它们与肿瘤细胞的动态相互作用有助于重塑TME,促进肿瘤生长和免疫调节。本综述总结了TME中TEC的研究,探讨了与肿瘤教育相关的机制,并讨论了它们在肿瘤进展和免疫治疗耐药中的作用。
此外,还综述了针对这些细胞的潜在治疗策略,这些策略可能补充当前的治疗方案。
In the past decade, immunotherapies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death 1 (PD-1), and PD-1 ligand (PD-L1) have been approved for solid tumors.
However, some patients demonstrate suboptimal clinical outcomes due to resistance. The tumor microenvironment (TME) significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells, including dendritic cells, T cells, B cells, macrophages, neutrophils, NK cells, and myeloid-derived suppressor cells (MDSCs). These non-tumor cells often exhibit two phenotypes with altered functions, and tumor cells drives their transition towards tumor promotion through tumor-education.
Tumor-educated cells (TECs) are cells influenced by tumor cells, which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anti-cancer therapies. These cells undergo modifications in response to signals from the tumor, which can influence their roles in tumor progression.
Their dynamic interactions with tumor cells contribute to the reshaping of the TME, facilitating cancer growth and immune modulation. This review summarizes research on TECs in TME, explores mechanisms related to tumor education, and discusses their role in tumor progression and immunotherapy resistance.
Additionally, potential therapeutic approaches targeting these cells are also reviewed, which may complement current treatment strategies.
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