1. Academic Validation
  2. Resolvins suppress tumor growth and enhance cancer therapy

Resolvins suppress tumor growth and enhance cancer therapy

  • J Exp Med. 2018 Jan 2;215(1):115-140. doi: 10.1084/jem.20170681.
Megan L Sulciner 1 2 3 Charles N Serhan 4 Molly M Gilligan 1 2 3 Dayna K Mudge 1 2 3 Jaimie Chang 1 2 3 Allison Gartung 1 2 3 Kristen A Lehner 1 2 3 Diane R Bielenberg 5 Birgitta Schmidt 6 Jesmond Dalli 7 Emily R Greene 1 2 3 Yael Gus-Brautbar 1 2 3 Julia Piwowarski 1 2 3 Tadanori Mammoto 5 David Zurakowski 8 9 Mauro Perretti 10 Vikas P Sukhatme 3 11 Arja Kaipainen 12 Mark W Kieran 13 14 Sui Huang 15 Dipak Panigrahy 16 2 3
Affiliations

Affiliations

  • 1 Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
  • 2 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
  • 3 Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
  • 4 Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA cserhan@bwh.harvard.edu.
  • 5 Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA.
  • 6 Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
  • 7 Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • 8 Department of Anesthesia, Boston Children's Hospital, Harvard Medical School, Boston, MA.
  • 9 Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA.
  • 10 The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, England, UK.
  • 11 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
  • 12 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • 13 Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA mark_kieran@dfci.harvard.edu.
  • 14 Department of Pediatric Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
  • 15 Institute of Systems Biology, Seattle, WA sui.huang@systemsbiology.org.
  • 16 Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA dpanigra@bidmc.harvard.edu.
Abstract

Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Thus, conventional Cancer therapy is inherently a double-edged sword. In this study, we show that tumor cells killed by chemotherapy or targeted therapy ("tumor cell debris") stimulate primary tumor growth when coinjected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin D1 (RvD1), RvD2, or RvE1. These mediators specifically inhibit debris-stimulated Cancer progression by enhancing clearance of debris via macrophage phagocytosis in multiple tumor types. Resolvins counterregulate the release of cytokines/chemokines, including TNFα, IL-6, IL-8, CCL4, and CCL5, by human macrophages stimulated with cell debris. These results demonstrate that enhancing endogenous clearance of tumor cell debris is a new therapeutic target that may complement cytotoxic Cancer therapies.

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