دورية أكاديمية
أعرض في EDS

Phosphodiesterase-5 inhibition reduces postoperative metastatic disease by targeting surgery-induced myeloid derived suppressor cell-dependent inhibition of Natural Killer cell cytotoxicity.

التفاصيل البيبلوغرافية
العنوان: Phosphodiesterase-5 inhibition reduces postoperative metastatic disease by targeting surgery-induced myeloid derived suppressor cell-dependent inhibition of Natural Killer cell cytotoxicity.
المؤلفون: Tai LH; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Alkayyal AA; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.; Department of Medical Laboratory Technology, University of Tabuk, Tabuk, Tabuk, Saudi Arabia., Leslie AL; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Sahi S; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Bennett S; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Surgery, University of Ottawa, Ottawa, ON, Canada., Tanese de Souza C; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Baxter K; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada., Angka L; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada., Xu R; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Kennedy MA; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Auer RC; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.; Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
المصدر: Oncoimmunology [Oncoimmunology] 2018 Mar 01; Vol. 7 (6), pp. e1431082. Date of Electronic Publication: 2018 Mar 01 (Print Publication: 2018).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101570526 Publication Model: eCollection Cited Medium: Print ISSN: 2162-4011 (Print) Linking ISSN: 21624011 NLM ISO Abbreviation: Oncoimmunology Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, TX : Landes Bioscience
مستخلص: Cancer surgery while necessary for primary tumor removal, has been shown to induce immune suppression and promote metastases in preclinical models and human cancer surgery patients. Activating the immune system and reversing immunosuppression have emerged as promising ways to treat cancer and they can be safely employed in the perioperative period. In this study, we evaluated the immunotherapeutic potential of phosphodiesterase-5 (PDE-5) inhibitors to target surgery-induced myeloid-derived suppressor cells (MDSC) and restore natural killer (NK) cell function in the clinically relevant perioperative period. Immunocompetent murine tumor models of major surgery were used to characterize the functional suppression of surgery-induced MDSC and to assess the in vivo efficacy of perioperative PDE5 inhibition. In cancer surgery patients with abdominal malignancies, we assessed postoperative NK cell function following co-culture with MDSC and PDE5 inhibition. Perioperative PDE5 inhibition reverses surgery-induced immunosuppression. In particular, sildenafil reduces surgery-derived granulocytic-MDSC (gMDSC) function through downregulation of arginase 1 (ARG1), IL4Ra and reactive oxygen species (ROS) expression, enabling NK cell antitumor cytotoxicity and reducing postoperative disease recurrence. By removing surgery-derived immunosuppressive mechanisms of MDSCs, sildenafil can be combined with the administration of perioperative influenza vaccination which targets NK cells to reduce postoperative metastasis. Importantly, sildenafil reverses MDSC suppression in cancer surgery patients. These findings demonstrate that PDE5 inhibitors reduce postoperative metastasis by their ability to inhibit surgery-induced MDSC. Further clinical studies are warranted to investigate the immunotherapeutic role of PDE5 inhibitors in combination with cancer surgery.
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فهرسة مساهمة: Keywords: NK cell cytotoxicity; Sildenafil; metastases; myeloid derived suppressor cells; postoperative immunosuppression
تواريخ الأحداث: Date Created: 20180607 Latest Revision: 20210112
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5980420
DOI: 10.1080/2162402X.2018.1431082
PMID: 29872554
قاعدة البيانات: MEDLINE
الوصف
تدمد:2162-4011
DOI:10.1080/2162402X.2018.1431082