Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells

Thi Tran (1) , Jean-Remi Lavillegrand (1) , Cedric Lereverend (2) , Bruno Esposito (1) , Lucille Cartier (2, 3) , Melanie Montabord (1) , Jaouen Tran-Rajau (1) , Marc Diedisheim (4) , Nadège Gruel (5) , Khadija Ouguerram (6) , Lea Paolini (1) , Olivia Lenoir (1) , Emmanuel Pinteaux (7) , Eva Brabencova (3) , Corinne Tanchot (1) , Pauline Urquia (1) , Jacqueline Lehmann-Che (8, 9) , Richard Le Naour (2) , Yacine Merrouche (2, 3) , Christian Stockmann (1, 10) , Ziad Mallat (1, 11) , Alain Tedgui (1) , Hafid Ait-Oufella (1) , Eric Tartour (1, 12) , Stephane Potteaux (1, 8)

1 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
2 IRMAIC - Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509
3 Institut Jean Godinot [Reims]
4 Hôpital Cochin [AP-HP]
5 U830 - Unité de génétique et biologie des cancers
6 PhAN - Physiopathologie des Adaptations Nutritionnelles
7 University of Manchester [Manchester]
8 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
9 AP-HP - Hopital Saint-Louis [AP-HP]
10 UZH - Universität Zürich [Zürich] = University of Zurich
11 CAM - University of Cambridge [UK]
12 HEGP - Hôpital Européen Georges Pompidou [APHP]

Abstract Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6C hi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer.

Domains: Subcellular Processes [q-bio.SC]

Thi Tran, Jean-Remi Lavillegrand, Cedric Lereverend, Bruno Esposito, Lucille Cartier, et al.. Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells. Nature Communications, 2022, 13 (1), pp.5399. ⟨10.1038/s41467-022-33034-0⟩. ⟨inserm-03788301⟩