Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Division of Oncology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
ESMO Open. 2020 May;5(3):e000647. doi: 10.1136/esmoopen-2019-000647.
The role of the adaptive immune system in the pathophysiology of cancer-associated venous thromboembolism (VTE) has not been investigated in detail. Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule responsible for immune evasion in several cancer entities, as expression on tumour cells silences the T cell-mediated immune response. Given the interrelation between inflammation, haemostasis and cancer, we aimed to investigate the association of players of the adaptive immunity (eg, lymphocytes, tumour PD-L1) with risk of VTE in patients with glioma, one of the most prothrombotic cancer types.
In this prospective observational single-centre cohort study, patients with newly diagnosed glioma or regrowth after resection were included. Primary endpoint was objectively confirmed VTE. At study inclusion, a blood draw was performed. Tumour PD-L1 expression was assessed via immunohistochemistry.
In total, 193 patients were included. PD-L1 expression in ≥1% of tumour cells was observed in 20/193 (10.4%) glioma. In multivariable cox-regression analysis, on adjustment for age, sex and WHO grade IV, systemic lymphocyte counts were significantly associated with risk of VTE (HR per 1 G/L increase (95% CI): 1.15 (1.03 to 1.29), p=0.013). In contrast, no significant difference in risk of VTE was found regarding the PD-L1 status: the cumulative 24 months probability of VTE was 17.0% in patients with no PD-L1 and 11.8% in those with PD-L1 expressing tumours (p=0.663).
In summary, PD-L1 expression was not associated with risk of VTE. Interestingly, peripheral lymphocytes, which are key players in adaptive immunity, were linked to an increased risk of glioma-associated VTE.
适应性免疫系统在癌症相关静脉血栓栓塞症(VTE)的病理生理学中的作用尚未得到详细研究。程序性细胞死亡配体 1(PD-L1)是一种免疫检查点分子,负责几种癌症实体的免疫逃逸,因为肿瘤细胞上的表达沉默了 T 细胞介导的免疫反应。鉴于炎症、止血和癌症之间的相互关系,我们旨在研究适应性免疫的参与者(例如淋巴细胞、肿瘤 PD-L1)与胶质母细胞瘤患者 VTE 风险之间的关联,胶质母细胞瘤是最易发生血栓形成的癌症类型之一。
在这项前瞻性观察性单中心队列研究中,纳入了新诊断为胶质母细胞瘤或切除后复发的患者。主要终点是客观证实的 VTE。在研究纳入时,进行了血液采集。通过免疫组织化学评估肿瘤 PD-L1 表达。
共纳入 193 例患者。在 193 例胶质母细胞瘤中,观察到≥1%的肿瘤细胞中 PD-L1 表达的有 20 例(10.4%)。在多变量 Cox 回归分析中,在校正年龄、性别和 WHO 分级 IV 后,系统淋巴细胞计数与 VTE 风险显著相关(每增加 1G/L 的 HR(95%CI):1.15(1.03 至 1.29),p=0.013)。相比之下,PD-L1 状态与 VTE 风险无显著差异:无 PD-L1 的患者 24 个月 VTE 的累积概率为 17.0%,而 PD-L1 表达肿瘤的患者为 11.8%(p=0.663)。
总之,PD-L1 表达与 VTE 风险无关。有趣的是,适应性免疫的关键参与者外周淋巴细胞与胶质母细胞瘤相关 VTE 的风险增加有关。