The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

• DOI: 10.1038/s41375-021-01201-9
• Publication Date: 2021-03-17T08:03:14Z
• Authors: Juan Garcia Valero; Alba Matas-Céspedes; Fabián Arenas; Vanina Rodriguez; Joaquim Carreras; Neus Serrat; Martina Guerrero-...; Anella Yahiaoui; Olga Balagué; Silvia Martin; Cristina Capdevila; Lluis Hernández; Laura Magnano; Alfredo Rivas-Del...; Stacey Tannheimer; Maria C. Cid; Elías Campo; Armando López-Gui...; Dolors Colomer; Patricia Pérez-Galán
• Keywords: Follicular lymphoma; Ex vivo; Follicular dendritic cells; Macrophage polarization; Pathogenesis

Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples HK dendritic cells (FDC) mimic germinal center, together mouse models, we have analyzed three-way crosstalk of FL-FDC-macrophages derived therapeutic opportunities. Ex vivo FL-FDC co-cultures (n = 19) in co-xenografts demonstrated that favors tumor growth and, via secretion CCL2 CSF-1, promotes monocyte recruitment, differentiation, polarization towards an M2-like protumoral phenotype. Moreover, FL-M2 displayed enhanced angiogenesis, dissemination, immunosuppression. Analysis CSF-1/CSF-1R pathway uncovered CSF-1 was significantly higher serum from grade 3A patients, high CSF-1R expression biopsies correlated 3A, reduced overall risk transformation. Furthermore, inhibition pexidartinib (PLX3397) preferentially affected M2-macrophage viability program disrupting positive crosstalk. CSF1-R caused M2 reduction repolarization M1 antitumor effect cooperating anti-CD20 rituximab. summary, these results support role indicate may be relevant prognostic factor novel target immunotherapy.