Department of Dermatology, Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), University Hospital Erlangen, Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054, Erlangen, Germany.
Department of Transfusion Medicine and Hemostaseology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), 91054, Erlangen, Germany.
Cancer Immunol Immunother. 2024 Nov 2;74(1):5. doi: 10.1007/s00262-024-03850-y.
Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies.
免疫检查点抑制剂 (ICI) 疗法有效地治疗了越来越多的癌症实体，但也会引起各种免疫相关的副作用 (irAEs)。最近的报告表明，ICI 诱导的全身炎症与血栓栓塞事件之间存在相关性，以及抗凝药物的联合应用会增加疗效。由于癌症患者本身发生血栓事件的风险较高，因此剖析和描述导致全身肿瘤治疗引起促凝作用的机制以及它们与抗肿瘤反应的潜在相互作用至关重要。共对 31 名接受 ICI（n=24）或 BRAF/MEK 抑制剂（n=7）治疗的晚期皮肤癌患者进行了前瞻性评估，在开始全身肿瘤治疗之前以及治疗后 7、20 和 40 天评估血液和凝血参数。分析并比较了两组之间的变化。此外，还研究了凝血参数对无进展、无复发和总生存期的影响。ICI 组在治疗一周后因子 VIII 活性显著升高（p<0.0225）；而蛋白 S 活性在整个观察期间降低。此外，在免疫治疗下，血管性血友病因子活性和组织因子浓度增加。BRAF/MEK 抑制剂治疗（BRAF/MEKi）也出现了类似的变化。ICI 治疗前基线水平较高的血管性血友病因子抗原和因子 VIII:C 与接受辅助免疫治疗的患者复发风险显著增加相关。这些发现表明 ICI 和 BRAF/MEKi 诱导促凝状态，以及凝血参数在 ICI 治疗疗效中的作用。
