Department of Psychiatry, Medical School, Universidade de Sao Paulo, Sao Paulo 05403-010, Brazil.
LIM 26, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil.
Int J Mol Sci. 2024 May 12;25(10):5275. doi: 10.3390/ijms25105275.
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.
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得其治疗具有挑战性。最近,我们的研究小组报告了一项涉及树突状细胞(DC)同种异体疫苗接种的前瞻性 II 期临床试验的有希望的结果。迄今为止,报告的 37 例中有 6 例仍未复发且存活。在这项研究中,我们专注于研究在手术切除时观察到的浸润免疫细胞的特征。我们使用基于神经网络的预测算法的分析模型来确定免疫变量对患者总生存期的潜在预后意义。反直觉的是,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指标。相比之下,该细胞亚群中 CD86 的高表达则是预后不良的指标。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性 TAMs 特征,预测接受树突状细胞疫苗接种的患者的总生存率。