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:Decoding the spatiotemporal dynamics of T cell immune landscapes in glioblastoma: remodeling precision combination therapies.
胶质母细胞瘤(GBM)中显著的瘤内异质性及其免疫抑制微环境高度动态的时空演化,是导致标准治疗(SOC)疗效有限的主要因素。
胶质母细胞瘤(GBM)中显著的瘤内异质性及其免疫抑制微环境高度动态的时空演化,是标准治疗(SOC)疗效有限的主要原因。尽管免疫治疗已彻底改变了许多实体瘤的治疗格局,但在GBM患者中产生的临床获益有限。这种有限的疗效与T细胞的丰度、分布和功能状态密切相关,T细胞是介导抗肿瘤免疫应答的核心效应细胞群。然而,既往研究在很大程度上聚焦于GBM中T细胞的静态特征,而调控其时空动态的机制仍不明确,从而阻碍了临床转化。在本综述中,我们描绘了GBM中T细胞的时空动态,并重新评估了免疫治疗失败的机制,从而识别潜在的治疗机会。此外,我们旨在为患者分层、开发调控T细胞时空动态的精准靶点以及GBM患者的个体化联合策略提供新的见解。
The profound intratumoral heterogeneity and the highly dynamic spatiotemporal evolution of its immunosuppressive microenvironment in glioblastoma (GBM) are major factors underlying the limited efficacy of the standard-of-care treatment (SOC). Although immunotherapy has revolutionized the treatment of many solid tumors, it has produced limited clinical benefit in patients with GBM. This limited efficacy is closely associated with the abundance, distribution, and functional state of T cells, which constitute the core effector population mediating antitumor immune responses. However, previous studies have largely focused on the static characteristics of T cells in GBM, whereas the mechanisms governing their spatiotemporal dynamics remain poorly defined, thereby impeding clinical translation. In this review, we delineate the spatiotemporal dynamics of T cells in GBM and re-evaluate the mechanisms underlying immunotherapy failure, thereby identifying potential therapeutic opportunities. Furthermore, we aim to provide new insights into patient stratification, the development of precise targets that modulate T-cell spatiotemporal dynamics, and personalized combination strategies for patients with GBM.
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