Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.

Fabien Guilloton (1) , Gersende Caron (1, 2) , Cédric Ménard (1, 2) , Céline Pangault (1, 2) , Patricia Amé-Thomas (1) , Joëlle Dulong (1) , John de Vos (3) , Delphine Rossille (4) , Catherine Henry (2) , Thierry Lamy (1) , Olivier Fouquet (5) , Thierry Fest (1) , Karin Tarte (1)

1 MiCa - Microenvironnement et cancer
2 HITC - Service d'Hématologie, Immunologie et de Thérapie Cellulaire
3 IRB - Institut de recherche en biothérapie
4 Modélisation Conceptuelle des Connaissances Biomédicales
5 Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes]

Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL-cell niche, thus emerging as a potential therapeutic target in this disease.

Domaines: Immunologie

Fabien Guilloton, Gersende Caron, Cédric Ménard, Céline Pangault, Patricia Amé-Thomas, et al.. Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.: CCL2 AND FOLLICULAR LYMPHOMA CELL NICHE. Blood, 2012, 119 (11), pp.2556-67. ⟨10.1182/blood-2011-08-370908⟩. ⟨inserm-00665887⟩