Abstract
Abstract Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Currently, approximately 40% of DLBCL patients treated with standard of care therapies, which include a combination of immunotherapy (rituximab; R) and chemotherapy (CHOP), will have disease that is refractory or will relapse. Tumor-associated macrophages can phagocytose opsonised DLBCL tumor cells and are therefore centrally important in determining therapeutic outcomes for patients treated with R-CHOP. Recent data from our lab and from others suggests that the modulation of sphingosine-1-phosphate (S1P) signalling may therapeutically benefit some patients with this tumor. Here, we have investigated the effects of S1P on macrophage functions relevant to DLBCL. We show that S1P signalling through the major receptor, S1P-receptor 1 (S1PR1), suppresses the phagocytosis of rituximab-opsonized DLBCL cells. However, we also show that chemotherapy potently induces monocyte recruitment to DLBCL tumors in vivo and that S1PR1 is a primary mediator of monocyte migration both in vitro and in vivo. According to our data, S1PR1 signalling inhibitors could improve the therapeutic efficacy of rituximab-based therapies for DLBCL patients. However, our data suggests that these drugs should be given only after chemotherapy and before rituximab administration so as to maximize the S1P-mediated recruitment of therapeutic macrophages to the tumor site. Citation Format: Tracey Adams Perry, Lauren Lupino, Katerina Vrzalikova, Navta Masand, Pamela R. Kearns, Paul G. Murray. Sphingosine-1-phosphate receptor 1 signalling modulates macrophage recruitment to diffuse large B cell lymphomas and the phagocytosis of rituximab-opsonized tumor cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2657.
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