Single-cell profiling identifies clinically relevant interactions between tumor associated macrophages and blood endothelial cells in diffuse large B cell lymphoma

Ferrant, J.; Le Gallou, S.; Padonou, F.; Leonard, S.; Papa, I.; Pangault, C.; Barthel, A.; Launay, V.; Manson, G.; Hoareau, B.; Deleurme, L.; Monvoisin, C.; Albaud, B.; Van Acker, N.; Laurent, C.; Llamas Gutierrez, F.; Michaud, H. A.; Bonnefoy, N.; Pecot, T.; Tarte, K.; Roussel, M.

doi:10.1101/2022.12.08.519637

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bioRxiv · 10.1101/2022.12.08.519637

Single-cell profiling identifies clinically relevant interactions between tumor associated macrophages and blood endothelial cells in diffuse large B cell lymphoma

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Abstract

Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) are the two most common B-cell lymphomas and are characterized by a dynamic crosstalk between tumor B cells and a heterogeneous tumor-supportive microenvironment, including immune, endothelial, and stromal components. Although their impact on the pathogenesis and prognosis of B-cell lymphoma has been acknowledged for years, tumor-associated macrophages (TAM) have not been extensively explored in DLBCL and FL. Herein, we investigate mononuclear phagocytes (MNP) heterogeneity at the single cell level and their potential co-regulation with the stromal and endothelial compartments in B-cell lymphoma lymph nodes compared to reactive secondary lymphoid organs, using a combination of mass cytometry, single cell RNA sequencing, and in silico approaches. We reveal a co-regulation between TAM and blood endothelial cells (BEC) in lymphoma. Moreover, we identify a specific interaction between Annexin A1 (ANXA1)-expressing BEC and formyl-peptide receptors (FPR1/2)-expressing monocytes/macrophages in DLBCL, which we confirm in situ by multiplex immunofluorescence and imaging mass cytometry. This crosstalk is associated to an immunosuppressive tumor microenvironment and an adverse prognosis in DLBCL.

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Ferrant, J., Le Gallou, S., Padonou, F., Leonard, S., Papa, I., Pangault, C., Barthel, A., Launay, V., Manson, G., Hoareau, B., Deleurme, L., Monvoisin, C., Albaud, B., Van Acker, N., Laurent, C., Llamas Gutierrez, F., Michaud, H. A., Bonnefoy, N., Pecot, T., Tarte, K., Roussel, M.. 2022-12-11. Single-cell profiling identifies clinically relevant interactions between tumor associated macrophages and blood endothelial cells in diffuse large B cell lymphoma. https://doi.org/10.1101/2022.12.08.519637

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