PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway

Li, Yulong; Xin, Guang; Li, Shiyi; Dong, Yuman; Zhu, Yuda; Yu, Xiuxian; Wan, Chengyu; Li, Fan; Wei, Zeliang; Wang, Yilan; Zhang, Kun; Chen, Qingqiu; Niu, Hai; Huang, Wen

doi:10.3389/fphar.2022.921414

Cited by 7 publications

(3 citation statements)

References 62 publications

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“…Interestingly, PD-L1-expressing platelets may partially explain the efficacy of ICIs even in PD-L1-negative tumors ( 169 ). Additionally, PD-L1 was found to activate platelets and amplify thrombosis ( 170 ).…”

Section: The Coagulome Reprograms the Tumor Microenvironment Towards ...mentioning

confidence: 99%

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy

Shafqat,

Omer,

Ahmed

et al. 2023

Front. Immunol.

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This review focuses on the immunosuppressive effects of tumor angiogenesis and coagulation on the tumor microenvironment (TME). We summarize previous research efforts leveraging these observations and targeting these processes to enhance immunotherapy outcomes. Clinical trials have documented improved outcomes when combining anti-angiogenic agents and immunotherapy. However, their overall survival benefit over conventional therapy remains limited and certain tumors exhibit poor response to anti-angiogenic therapy. Additionally, whilst preclinical studies have shown several components of the tumor coagulome to curb effective anti-tumor immune responses, the clinical studies reporting combinations of anticoagulants with immunotherapies have demonstrated variable treatment outcomes. By reviewing the current state of the literature on this topic, we address the key questions and future directions in the field, the answers of which are crucial for developing effective strategies to reprogram the TME in order to further the field of cancer immunotherapy.

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Section: The Coagulome Reprograms the Tumor Microenvironment Towards ...mentioning

confidence: 99%

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy

Shafqat,

Omer,

Ahmed

et al. 2023

Front. Immunol.

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“…The cancer cells can activate the coagulation cascade and other prothrombotic processes in the host cell in absence of other predisposing factors for thrombosis. activation and arterial thrombosis [4], but several studies did not found a relationship between the presence of PD-L1 mutation and venous thrombosis [5,6].…”

Section: Discussionmentioning

confidence: 99%

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Tiron

2022

J Biomed Res Environ Sci

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Background: Pulmonary Embolism (PE) is a life-threatening condition with annual incidence ranging from 39 to 115 cases per 100,000 population [1]. Along with many other causes, neoplasia is one of the highest risk factors for pancreatic, lung, gastric, cerebral and haematological cancer [2]. Patients with neoplasia often have venous thromboembolism (VTE) during the course of the disease, but occasionally neoplasia is diagnosed as secondary to VTE. Case Presentation: A 55-year-old man known with high blood pressure and dyslipidaemia is diagnosed with bilateral distal Deep Venous Thrombosis (DVT) and treated with a factor Xa inhibitor. Two months later he is admitted for fatigue, dry cough, unwanted weight loss of approximately 5kg for a month and progressive exertion dyspnea. The echocardiographic examination reveals dilated right chambers with thrombus in the Right Ventricle (RV). The suspicion of pulmonary embolism it was confirmed on thoracic contrast CT examination. Large bilateral mediastinal adenopathies and a right lung nodule were also visualised on lung CT scan. The patient was treated with unfractionated heparin, slow-acting nitrate, aspirin, calcium blocker, with the disappearance of the thrombus from the right ventricle. Bronchoscopy showed a lesion near the right main bronchus. The diagnosis of pulmonary adenocarcinoma is confirmed histopathologically on the sample obtained at bronchoscopy and from the mediastinal lymph node obtained at mediastinoscopy. The patient was referred to the oncology service for specialised treatment. Conclusion: VTE under anticoagulant treatment should always raise some suspicions and other causes should be sought. Undiagnosed neoplasms , drug resistance or drug interactions, thrombophilias are some of the causes that should be suspected in case of thrombosis under therapeutic anticoagulant.

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“…NLRP3 affected platelet αIIbβ3 outside-in signal transduction, an essential process for hemostasis and thrombosis, which might be mediated by IL-1β, as significantly reduced IL-1β release was found in NLRP3-deficient platelets ( 96 ). Furthermore, in thrombin activated-platelets, the caspase-3/GSDME pathway was upregulated, further regulating platelet integrin αIIbβ3 activation ( 97 ).…”

Section: Pyroptosis-induced Hemostasis Activation In Sepsismentioning

confidence: 99%

Role of pyroptosis in hemostasis activation in sepsis

et al. 2023

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Sepsis is frequently associated with hemostasis activation and thrombus formation, and systematic hemostatic changes are associated with a higher risk of mortality. The key events underlying hemostasis activation during sepsis are the strong activation of innate immune pathways and the excessive inflammatory response triggered by invading pathogens. Pyroptosis is a proinflammatory form of programmed cell death, that defends against pathogens during sepsis. However, excessive pyroptosis can lead to a dysregulation of host immune responses and organ dysfunction. Recently, pyroptosis has been demonstrated to play a prominent role in hemostasis activation in sepsis. Several studies have demonstrated that pyroptosis participates in the release and coagulation activity of tissue factors. In addition, pyroptosis activates leukocytes, endothelial cells, platelets, which cooperate with the coagulation cascade, leading to hemostasis activation in sepsis. This review article attempts to interpret the molecular and cellular mechanisms of the hemostatic imbalance induced by pyroptosis during sepsis and discusses potential therapeutic strategies.

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PD-L1 Regulates Platelet Activation and Thrombosis via Caspase-3/GSDME Pathway

Cited by 7 publications

References 62 publications

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Role of pyroptosis in hemostasis activation in sepsis

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