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Neutrophil-activating therapy for the treatment of cancer.
Linde, Ian L; Prestwood, Tyler R; Qiu, Jingtao; Pilarowski, Genay; Linde, Miles H; Zhang, Xiangyue; Shen, Lei; Reticker-Flynn, Nathan E; Chiu, David Kung-Chun; Sheu, Lauren Y; Van Deursen, Simon; Tolentino, Lorna L; Song, Wen-Chao; Engleman, Edgar G.
Afiliação
  • Linde IL; Program in Immunology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Prestwood TR; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Qiu J; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Pilarowski G; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Linde MH; Program in Immunology, Stanford University, Stanford, CA 94305, USA.
  • Zhang X; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Shen L; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Reticker-Flynn NE; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Chiu DK; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Sheu LY; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Van Deursen S; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Tolentino LL; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Song WC; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Engleman EG; Program in Immunology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: edengleman@stanford.edu.
Cancer Cell ; 41(2): 356-372.e10, 2023 02 13.
Article em En | MEDLINE | ID: mdl-36706760
Despite their cytotoxic capacity, neutrophils are often co-opted by cancers to promote immunosuppression, tumor growth, and metastasis. Consequently, these cells have received little attention as potential cancer immunotherapeutic agents. Here, we demonstrate in mouse models that neutrophils can be harnessed to induce eradication of tumors and reduce metastatic seeding through the combined actions of tumor necrosis factor, CD40 agonist, and tumor-binding antibody. The same combination activates human neutrophils in vitro, enabling their lysis of human tumor cells. Mechanistically, this therapy induces rapid mobilization and tumor infiltration of neutrophils along with complement activation in tumors. Complement component C5a activates neutrophils to produce leukotriene B4, which stimulates reactive oxygen species production via xanthine oxidase, resulting in oxidative damage and T cell-independent clearance of multiple tumor types. These data establish neutrophils as potent anti-tumor immune mediators and define an inflammatory pathway that can be harnessed to drive neutrophil-mediated eradication of cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article