Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Malte Beckmann, Julian Schlüter, Michael Erdmann, Rafaela Kramer, Sarah Cunningham, Holger Hackstein, Robert Zimmermann, Lucie Heinzerling
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Abstract

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.

凝血与免疫疗法和 BRAF/MEK 抑制剂疗法之间的相互依存关系:一项前瞻性研究的结果。
免疫检查点抑制剂(ICI)疗法可有效治疗范围不断扩大的癌症实体,但会诱发各种免疫相关副作用(irAEs)。最近的报告表明,ICI 引发的全身炎症与血栓栓塞事件之间存在相关性,而且联合使用抗凝剂可提高疗效。由于癌症患者本身发生血栓事件的风险较高,因此剖析和描述全身性肿瘤疗法诱发促凝血效应的机制及其与抗肿瘤反应的潜在相互作用至关重要。研究人员对接受 ICIs(24 例)或 BRAF/MEK 抑制剂(7 例)治疗的 31 例晚期皮肤癌患者进行了纵向血液和凝血参数评估,这些参数包括开始接受系统性肿瘤治疗前、开始接受系统性肿瘤治疗后 7 天、20 天和 40 天的参数。对两组的变化进行了分析和比较。此外,还研究了凝血参数对无进展生存期、无复发生存期和总生存期的影响。治疗一周后,ICI 组的因子 VIII 活性明显增加(p 0.0225);而在整个观察期间,蛋白 S 活性降低。此外,在免疫疗法中,von Willebrand因子活性和组织因子浓度也有所增加。BRAF/MEK抑制剂疗法(BRAF/MEKi)也发生了类似的变化。在开始接受 ICI 治疗前,von Willebrand 因子抗原和因子 VIII:C 的基线水平升高与接受辅助免疫疗法的患者复发风险显著升高相关。研究结果表明,ICI 和 BRAF/MEKi 会诱导促凝血状态,凝血参数在 ICI 疗法的疗效中发挥作用。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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