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The Oncogenic lipid sphingosine-1-phosphate impedes the phagocytosis of tumor cells by M1 macrophages in diffuse large B cell lymphoma

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posted on 2024-02-07, 11:39 authored by Tracey A. Perry, Navta Masand, Katerina Vrzalikova, Matthew Pugh, Wenbin Wei, Robert Hollows, Katerina Bouchalova, Mahdi NohtaniMahdi Nohtani, Éanna FennellÉanna Fennell, Jan Bouchal, Pamela Kearns, Paul MurrayPaul Murray

Abstract: Background: A total of 30–40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells. However, we lack insights into the factors responsible for the recruitment and functionality of macrophages in DLBCL tumors. Methods: We have studied the effects of the immunomodulatory lipid sphingosine-1-phosphate (S1P) on macrophage activity in DLBCL, both in vitro and in animal models. Results: We show that tumor-derived S1P mediates the chemoattraction of both monocytes and macrophages in vitro and in animal models, an effect that is dependent upon the S1P receptor S1PR1. However, S1P inhibited M1 macrophage-mediated phagocytosis of DLBCL tumor cells opsonized with the CD20 monoclonal antibodies rituximab and ofatumumab, an effect that could be reversed by an S1PR1 inhibitor. Conclusions: Our data show that S1P signaling can modulate macrophage recruitment and tumor cell killing by anti-CD20 monoclonal antibodies in DLBCL The administration of S1PR1 inhibitors could enhance the phagocytosis of tumor cells and improve outcomes for patients.

History

Publication

Cancers 16(3), 574

Publisher

MDPI

Other Funding information

Blood Cancer UK (No. 13045), a CCLG/Little Princess Trust Project Grant (CCLGA 2017 18) European Regional Development Fund Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) and by the Czech Ministry of Health (DRO: FNOL00098892)

Also affiliated with

  • Bernal Institute
  • Health Research Institute (HRI)

Sustainable development goals

  • (3) Good Health and Well-being

Department or School

  • School of Medicine

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