Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Via P. Maroncelli 40, 47014, Meldola, Italy.
Preclinic and Osteoncology Unit, Bioscience Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014, Meldola, Italy.
J Neurooncol. 2023 Aug;164(1):55-64. doi: 10.1007/s11060-023-04357-9. Epub 2023 Aug 16.
The aims of our retrospective study investigated the role of immune system in glioblastoma (GBM), which is the most aggressive primary brain tumor in adults characterized by a poor prognosis. The recurrence rate remains high, probably due to "immune-desert" tumor microenvironment (TME) making GBM hidden from the anti-tumoral immune clearance. Considering this, we aimed to create a panel of prognostic markers from blood and tumor tissue correlating with overall survival (OS) and progression-free survival (PFS).
Firstly, we analyzed the inflammatory markers NLR and PLR as the ratio of the absolute neutrophil count and absolute platelet count by the absolute lymphocyte count respectively, collected at different time points in the peripheral blood of 95 patients. Furthermore, in 31 patients of the same cohort, we analyzed the formalin-fixed paraffin embedded samples to further compare the impact of circulating and inflammatory markers within the TME.
Patients aged < 60 years and with methylated MGMT showed better OS. While, pre-chemotherapy Systemic Inflammatory Index (SII) < 480 was related to a better OS and PFS, we observed that only CD68+macrophage and CD66b+neutrophils expressed in vascular/perivascular area (V) showed a statistically significant prognostic role in median OS and PFS.
Thus, we underscored a role of SII as predictive value of response to STUPP protocol. Regarding the TME-related markers, we suggested to take into consideration for future studies with new immunotherapy combinations, each component relating to expression of immune infiltrating subsets.
我们的回顾性研究旨在探讨免疫系统在胶质母细胞瘤(GBM)中的作用,GBM 是成人中最具侵袭性的原发性脑肿瘤,预后较差。复发率仍然很高,可能是由于“免疫荒漠”肿瘤微环境(TME)使 GBM 逃避了抗肿瘤免疫清除。考虑到这一点,我们旨在从血液和肿瘤组织中创建一组与总生存期(OS)和无进展生存期(PFS)相关的预后标志物。
首先,我们分析了炎症标志物 NLR 和 PLR,分别为外周血中性粒细胞计数和血小板计数的绝对值与淋巴细胞计数的绝对值之比,共分析了 95 名患者不同时间点的外周血样本。此外,在同一队列的 31 名患者中,我们分析了福尔马林固定石蜡包埋样本,以进一步比较循环和 TME 内炎症标志物的影响。
年龄<60 岁和甲基化 MGMT 患者的 OS 更好。而化疗前系统性炎症指数(SII)<480 与更好的 OS 和 PFS 相关,我们观察到仅血管/血管周围区(V)中表达的 CD68+巨噬细胞和 CD66b+中性粒细胞在中位 OS 和 PFS 方面具有统计学显著的预后作用。
因此,我们强调 SII 作为对 STUPP 方案反应的预测价值。关于 TME 相关标志物,我们建议在未来的免疫治疗联合研究中考虑这些标志物,每个标志物都与免疫浸润亚群的表达有关。