Department of Neurosurgery and Neuro-Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
Int Immunopharmacol. 2024 Oct 25;140:112797. doi: 10.1016/j.intimp.2024.112797. Epub 2024 Jul 30.
Reoperation is a treatment option for recurrent gliomas, yet factors impacting survival following reoperation remain poorly defined. Tumor immunity is profoundly associated with disease progression. Here, we analyze the immune status characteristics and their prognostic implications in recurrent gliomas.
Intratumoral and peripheral immune characteristics between primary and recurrent gliomas were compared by conducting immunohistological staining and hematological examination with our in-house samples, and analyzing bulk and single-cell sequencing data from publicly available sources. Survival analysis was conducted to identify immunological markers with prognostic significances.
We observed a significant reduction in peripheral lymphocyte count, while an elevation in neutrophil-to-lymphocyte ratio (NLR) and red cell distribution width-to-platelet ratio (RPR) in patients with recurrent gliomas than in newly-diagnosed patients. Higher NLR and RPR indicated worse survival following reoperation in recurrent patients. Transcriptomic and immunohistological analysis showed an increased infiltration of tumor-associated macrophages (TAMs) and CD8 T cell in recurrent gliomas compared to primary gliomas in both IDH-wildtype and mutant subtypes. Moreover, the abundance of TAMs emerged as an independent indicator for an inferior prognosis in recurrent gliomas. Single-cell profiling revealed a significant heterogeneity in the phenotypes of TAMs between primary and recurrent gliomas. Notably, TAMs enriched in recurrent gliomas exhibited elevated expression of interferon-γ-induced genes, multiple immunosuppressive molecules (TGFB1, CD276), and increased activity in glycose and lipid metabolism, indicating metabolic reprogramming.
Recurrent gliomas demonstrate augmented immune cell infiltration, but they fail to overcome TAMs-induced immunosuppression. Immunosuppressive indices, including TAM abundance, peripheral NLR and RPR, have prognostic implications for recurrent gliomas.
对于复发性神经胶质瘤，再次手术是一种治疗选择，但影响再次手术后生存的因素仍未明确定义。肿瘤免疫与疾病进展密切相关。在这里，我们分析了复发性神经胶质瘤的免疫状态特征及其预后意义。
通过对我们的内部样本进行免疫组织化学染色和血液学检查，并分析来自公共来源的批量和单细胞测序数据，比较了原发性和复发性神经胶质瘤之间的肿瘤内和外周免疫特征。进行生存分析以确定具有预后意义的免疫标志物。
我们观察到复发性神经胶质瘤患者的外周淋巴细胞计数明显减少，而中性粒细胞与淋巴细胞比值（NLR）和红细胞分布宽度与血小板比值（RPR）升高。复发性患者中 NLR 和 RPR 较高表明再次手术后生存较差。转录组学和免疫组织化学分析显示，与原发性神经胶质瘤相比，IDH 野生型和突变型亚型的复发性神经胶质瘤中肿瘤相关巨噬细胞（TAMs）和 CD8 T 细胞浸润增加。此外，TAMs 的丰度成为复发性神经胶质瘤预后不良的独立指标。单细胞分析显示，原发性和复发性神经胶质瘤之间 TAMs 的表型存在显著异质性。值得注意的是，在复发性神经胶质瘤中富集的 TAMs 表现出干扰素-γ诱导基因、多种免疫抑制分子（TGFB1、CD276）的表达上调，以及糖和脂质代谢活性增加，表明代谢重编程。
复发性神经胶质瘤表现出增强的免疫细胞浸润，但未能克服 TAMs 诱导的免疫抑制。免疫抑制指数，包括 TAM 丰度、外周 NLR 和 RPR，对复发性神经胶质瘤具有预后意义。
