Myeloid landscape profiling identifies DLBCL-specific suppressive macrophages colocalized with blood endothelial cells
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the 2 most common B-cell lymphomas and are characterized by a dynamic crosstalk between tumor B cells and a heterogeneous, tumor-supportive microenvironment, such as immune, endothelial, and stromal components. Despite their recognized impact on the pathogenesis and prognosis of B-cell lymphoma, tumor-associated macrophages (TAM) have not been extensively explored in these diseases. In this study, we investigated mononuclear phagocyte (MNP) heterogeneity at the single-cell level and the activation profile of MNP, stromal, and endothelial compartments, in B-cell lymphoma lymph nodes compared to reactive secondary lymphoid organs. This was achieved using a combination of mass cytometry, single-cell RNA sequencing, in silico and spatial imaging approaches. Our findings revealed a lymphoma-specific pattern of TAM and blood endothelial cell (BEC) coactivation. Furthermore, we identified in DLBCL a spatial interaction between Annexin A1 (ANXA1)-expressing BEC and formyl-peptide receptor (FPR1/2) and S100A9-expressing monocytes/macrophages. This crosstalk is associated with an immunosuppressive tumor microenvironment and an adverse prognosis in patients with DLBCL.
Authors
- Céline Monvoisin (ORCID: https://orcid.org/0000-0003-1511-7888)
- Nathalie Van Acker (ORCID: https://orcid.org/0000-0003-0420-5081)
- Charles Brottier
- Henri‐Alexandre Michaud (ORCID: https://orcid.org/0000-0002-6165-1929)
- Céline Pangault (ORCID: https://orcid.org/0000-0003-3978-2209)
- Karin Tarte (ORCID: https://orcid.org/0000-0002-6809-917X)
- Margaret A. Shipp (ORCID: https://orcid.org/0000-0002-3949-6897)
- Laurent Deleurme
- Juliette Ferrant (ORCID: https://orcid.org/0000-0003-2193-4104)
- Anne Barthel
- Ilenia Papa (ORCID: https://orcid.org/0000-0003-3167-7623)
- Guillaume Manson (ORCID: https://orcid.org/0000-0003-4280-7825)
- Bénédicte Hoareau‐Coudert (ORCID: https://orcid.org/0000-0002-6575-7085)
- Thierry Pécot (ORCID: https://orcid.org/0000-0003-0772-9753)
- Simon Le Gallou (ORCID: https://orcid.org/0009-0003-4758-2423)
- Simon Léonard (ORCID: https://orcid.org/0000-0002-6437-5800)
- Vincent Launay
- Camille Laurent (ORCID: https://orcid.org/0000-0002-5375-7512)
- Francine Padonou
- Nathalie Bonnefoy (ORCID: https://orcid.org/0000-0003-4814-6722)
- Charlotte Dubec‐Fleury
- Francisco Llamas Gutierrez
- Mikaël Roussel (ORCID: https://orcid.org/0000-0002-9741-0668)
- Benoit Alaud
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Sorbonne Nouvelle (FR)
- Université Paris Sciences et Lettres (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Université Rennes 2 (FR)
- Sorbonne Université (FR)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Centre d'Économie de la Sorbonne (FR)
- Centre Hospitalier de Bretagne Sud (FR)
- Centre Hospitalier de Saint-Brieuc (FR)
- Dana-Farber Cancer Institute (US)
- Pitié-Salpêtrière Hospital (FR)
- Établissement Français du Sang (FR)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Services déconcentrés d'appui à la recherche Occitanie-Montpellier (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Structure Fédérative de Recherche en Biologie et Santé de Rennes (FR)
- Université Paris 1 Panthéon-Sorbonne (FR)
- Université de Rennes (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Blood Advances
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1182/bloodadvances.2024015689
- Citations
- 3
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.39