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

Garcia Valero, Juan; Matas-Céspedes, Alba; Arenas, Fabián; Rodriguez, Vanina; Carreras, Joaquim; Serrat, Neus; Guerrero-Hernández, Martina; Yahiaoui, Anella; Balagué, Olga; Martin, Silvia; Capdevila, Cristina; Hernández, Lluis; Magnano, Laura; Rivas-Delgado, Alfredo; Tannheimer, Stacey; Cid, Maria C.; Campo, Elias; López Guillermo, Armando; Colomer Pujol, Dolors; Pérez-Galán, Patricia

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

Mostra el registre complet Registre parcial de l'ítem

dc.contributor.author Garcia Valero, Juan
dc.contributor.author Matas-Céspedes, Alba
dc.contributor.author Arenas, Fabián
dc.contributor.author Rodriguez, Vanina
dc.contributor.author Carreras, Joaquim
dc.contributor.author Serrat, Neus
dc.contributor.author Guerrero-Hernández, Martina
dc.contributor.author Yahiaoui, Anella
dc.contributor.author Balagué, Olga
dc.contributor.author Martin, Silvia
dc.contributor.author Capdevila, Cristina
dc.contributor.author Hernández, Lluis
dc.contributor.author Magnano, Laura
dc.contributor.author Rivas-Delgado, Alfredo
dc.contributor.author Tannheimer, Stacey
dc.contributor.author Cid, Maria C.
dc.contributor.author Campo, Elias
dc.contributor.author López Guillermo, Armando
dc.contributor.author Colomer Pujol, Dolors
dc.contributor.author Pérez-Galán, Patricia
dc.date.accessioned 2022-05-17T10:57:50Z
dc.date.available 2022-05-17T10:57:50Z
dc.date.issued 2021
dc.description.abstract Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and derived therapeutic opportunities. Ex vivo primary FL-FDC co-cultures (n = 19) and in vivo mouse co-xenografts demonstrated that FL-FDC crosstalk favors tumor growth and, via the secretion of CCL2 and CSF-1, promotes monocyte recruitment, differentiation, and polarization towards an M2-like protumoral phenotype. Moreover, FL-M2 co-cultures displayed enhanced angiogenesis, dissemination, and immunosuppression. Analysis of the CSF-1/CSF-1R pathway uncovered that CSF-1 was significantly higher in serum from grade 3A FL patients, and that high CSF-1R expression in FL biopsies correlated with grade 3A, reduced overall survival and risk of transformation. Furthermore, CSF-1R inhibition with pexidartinib (PLX3397) preferentially affected M2-macrophage viability and polarization program disrupting FL-M2 positive crosstalk. In vivo CSF1-R inhibition caused M2 reduction and repolarization towards M1 macrophages and antitumor effect cooperating with anti-CD20 rituximab. In summary, these results support the role of macrophages in FL pathogenesis and indicate that CSF-1R may be a relevant prognostic factor and a novel therapeutic target cooperating with anti-CD20 immunotherapy.
dc.description.sponsorship Grants that contributed to this work included: Gilead Sciences Research Funded Agreement, Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa” for SAF2014/57708R and SAF2017/ 88275R to PP-G and MCC, RTI2018-094584-B-I00 to DC, CIBERONC (CB16/12/00334 and CB16/12/00225), and finally Generalitat de Catalunya support for AGAUR 2017SGR1009 to DC
dc.format.mimetype application/pdf
dc.identifier.citation Garcia Valero J, Matas-Céspedes A, Arenas F, Rodriguez V, Carreras J, Serrat N et al. The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma. Leukemia. 2021 Sep;35(9):2635-2649. DOI:10.1038/s41375-021-01201-9
dc.identifier.doi http://dx.doi.org/10.1038/s41375-021-01201-9
dc.identifier.issn 1476-5551
dc.identifier.uri http://hdl.handle.net/10230/53116
dc.language.iso eng
dc.publisher Springer Nature
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-57708R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-88275R
dc.rights © Juan Garcia Valero et al. 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Limfoma fol·licular
dc.subject.other Càncer -- Tractament
dc.title The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))