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:Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.
Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.
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胶质母细胞瘤(GBM)是最常见的原发性恶性脑肿瘤,占成人所有癌症的2%。其位置、细胞和分子异质性,以及高度浸润性,使其治疗具有挑战性。最近,我们的研究组报告了一项涉及同种异体树突状细胞(DCs)疫苗的前瞻性II期临床试验的有希望结果。迄今为止,报告的三十七例病例中有六例仍然存活且无肿瘤复发。在这项研究中,我们重点关注手术切除时观察到的浸润免疫细胞的表征。采用基于神经网络的预测算法的分析模型来确定免疫学变量对患者总生存期的潜在预后意义。与直觉相反,肿瘤相关巨噬细胞(TAMs)的免疫表型分析显示,细胞外标志物PD-L1是总生存期的阳性预测因子。相反,该细胞亚群中CD86表达升高则成为阴性预后指标。从根本上说,这里概述的神经网络算法允许根据临床参数和肿瘤切除时观察到的浸润TAMs谱,预测接受树突状细胞疫苗接种的患者在总生存期方面的反应性。
Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection.
An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival.
In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.
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