CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma.
Isolated Peptide from Spider Venom Modulates Dendritic Cells In Vitro: A Possible Application in Oncoimmunotherapy for Glioblastoma.
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树突状细胞(DCs)疫苗是一种潜在的肿瘤免疫治疗工具。然而,已知该治疗策略在实体瘤中未能成功,这使得免疫佐剂的开发高度相关。近期,我们证明Phoneutria nigriventer蜘蛛毒液(PnV)成分对胶质母细胞瘤(GB)具有细胞毒性,并能激活巨噬细胞向抗肿瘤表型转化。
然而,这些分子对适应性免疫应答的影响尚未被评估。本研究旨在体外测试PnV及其纯化组分对DCs的作用。为此,从雄性C57BL6小鼠中收集骨髓前体细胞,分化为DCs,并用毒液或PnV分离组分(F1-分子< 3 kDa,F2-3至10 kDa和F3->10 kDa)处理,联合或不联合人GB裂解物共刺激。
结果显示,主要是F1能够激活DCs,增加激活依赖性表面标志物(CD86)和细胞因子释放(IL-1β、TNF-α),此外还诱导成熟DCs的典型形态。从F1纯化中,一种名为LW9的分子最为有效,质谱分析显示其为一种肽。
本研究结果表明,该分子可能是一种免疫佐剂,有望应用于治疗GB的DC疫苗。
Dendritic cells (DCs) vaccine is a potential tool for oncoimmunotherapy.
However, it is known that this therapeutic strategy has failed in solid tumors, making the development of immunoadjuvants highly relevant. Recently, we demonstrated that Phoneutria nigriventer spider venom (PnV) components are cytotoxic to glioblastoma (GB) and activate macrophages for an antitumor profile.
However, the effects of these molecules on the adaptive immune response have not yet been evaluated. This work aimed to test PnV and its purified fractions in DCs in vitro. For this purpose, bone marrow precursors were collected from male C57BL6 mice, differentiated into DCs and treated with venom or PnV-isolated fractions (F1-molecules < 3 kDa, F2-3 to 10 kDa and F3->10 kDa), with or without costimulation with human GB lysate.
The results showed that mainly F1 was able to activate DCs, increasing the activation-dependent surface marker (CD86) and cytokine release (IL-1β, TNF-α), in addition to inducing a typical morphology of mature DCs. From the F1 purification, a molecule named LW9 was the most effective, and mass spectrometry showed it to be a peptide. The present findings suggest that this molecule could be an immunoadjuvant with possible application in DC vaccines for the treatment of GB.
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