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.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Comprehensive analysis of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2): A potential novel pan-cancer immune checkpoint.
我们的数据表明,TNFAIP8L2可能是一种跨不同肿瘤类型的新型免疫检查点生物标志物,尤其是在LAML、LGG、KIRC和UVM中,并可能进一步作为免疫治疗的潜在靶点。
肿瘤坏死因子诱导蛋白8样2(TIPE2)由TNFAIP8L2编码,是一种新发现的天然免疫和获得性免疫负调控因子,在维持免疫稳态中发挥关键作用。近年来,CAR-NK免疫细胞治疗作为一种新型癌症治疗策略,已成为主要研究热点。TIPE2是免疫细胞成熟和抗肿瘤免疫的潜在检查点分子,可作为新型基于NK细胞的免疫治疗方法。在本研究中,我们探索了TNFAIP8L2在各种肿瘤类型中的表达,发现TNFAIP8L2在大多数肿瘤类型中高表达,并与预后相关。生存分析显示,TNFAIP8L2表达可预测宫颈鳞状细胞癌(CESC)、肉瘤(SARC)和皮肤黑色素瘤(SKCM)的生存改善。相反,TNFAIP8L2表达预测急性髓系白血病(LAML)、低级别胶质瘤(LGG)、肾透明细胞癌(KIRC)和葡萄膜黑色素瘤(UVM)的生存较差。干性特征和免疫细胞浸润分析表明,TNFAIP8L2与癌症干细胞指数以及巨噬细胞和树突状细胞浸润增加显著相关。我们的数据表明,TNFAIP8L2可能是不同肿瘤类型中的新型免疫检查点生物标志物,尤其是在LAML、LGG、KIRC和UVM中,并可能进一步作为免疫治疗的潜在靶点。
Tumor necrosis factor- -inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly identified negative regulator of natural and acquired immunity that plays a critical function in maintaining immune homeostasis. Recently, CAR-NK immune cell therapy has been a focus of major research efforts as a novel cancer therapeutic strategy. TIPE2 is a potential checkpoint molecule for immune cell maturation and antitumor immunity that could be used as a novel NK cell-based immunotherapeutic approach. In this study, we explored the expression of TNFAIP8L2 across various tumor types and found that TNFAIP8L2 was highly expressed in most tumor types and correlated with prognosis. Survival analysis showed that TNFAIP8L2 expression was predictive of improved survival in cervical-squamous-cell-carcinoma (CESC), sarcoma (SARC) and skin-cutaneous-melanoma (SKCM). Conversely, TNFAIP8L2 expression predicted poorer survival in acute myeloid leukemia (LAML), lower-grade-glioma (LGG), kidney-renal-clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). Analysis of stemness features and immune cell infiltration indicated that TNFAIP8L2 was significantly associated with cancer stem cell index and increased macrophage and dendritic cell infiltration. Our data suggest that TNFAIP8L2 may be a novel immune checkpoint biomarker across different tumor types, particularly in LAML, LGG, KIRC and UVM, and may have further utility as a potential target for immunotherapy.
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