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:Harnessing innate immunity against glioblastoma microenvironment.
Harnessing innate immunity against glioblastoma microenvironment.
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胶质母细胞瘤(GBM)具有由固有免疫机制主导的深度免疫抑制性肿瘤微环境(TME)。肿瘤相关巨噬细胞(TAM)、小胶质细胞和髓源性抑制细胞(MDSC)构成主要的免疫抑制轴,通过细胞因子分泌(IL-10、TGF-β)、代谢重编程和抑制细胞毒性免疫来促进肿瘤进展。这些固有免疫细胞不仅促进免疫逃逸,还损害适应性T细胞应答,限制了当前免疫疗法的疗效。新出现的证据凸显了通过TAM重极化、MDSC清除和NK细胞激活来靶向固有免疫以重塑免疫抑制性TME的治疗潜力。本综述总结了固有免疫在GBM发病机制中的关键作用,并探讨了将固有免疫调节与检查点阻断、溶瘤病毒疗法和代谢干预相结合的新型联合策略,以克服这一致死性恶性肿瘤的治疗耐药性。
Glioblastoma (GBM) possesses a profoundly immunosuppressive tumor microenvironment (TME) dominated by innate immune mechanisms. Tumor-associated macrophages (TAMs), microglia, and myeloid-derived suppressor cells (MDSCs) constitute the major immunosuppressive axis, promoting tumor progression through cytokine secretion (IL-10, TGF-β), metabolic reprogramming, and inhibition of cytotoxic immunity. These innate immune cells not only facilitate immune evasion but also impair adaptive T-cell responses, limiting the efficacy of current immunotherapies.
Emerging evidence highlights the therapeutic potential of targeting innate immunity via TAM repolarization, MDSC depletion, and NK cell activation to reshape the immunosuppressive TME. This review summarizes the pivotal role of innate immunity in GBM pathogenesis and explores novel combinatorial strategies that integrate innate immune modulation with checkpoint blockade, oncolytic virotherapy, and metabolic interventions to overcome therapeutic resistance in this lethal malignancy.
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