title: Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+T-cells favoring anti-tumor immunity.
abstract: Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8+T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation. Our findings suggest that D3R in DCs constitutes a new therapeutic target to strengthen anti-tumor immunity.
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas y Químicas, Facultad de Ciencia, Universidad San Sebastián, Providencia, 7510157 Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Figueroa
authors.affiliation: Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Gálvez-Cancino
authors.affiliation: Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Cesar
authors.initials: C
authors.lastname: Oyarce
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Contreras
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Prado
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Catalina
authors.initials: C
authors.lastname: Valeria
authors.affiliation: Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cruz
authors.affiliation: Laboratorio de Inmunoterapia Génica, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Lladser
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272 Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile. Electronic address: rpacheco@cienciavida.org.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pacheco
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050637:Receptors, Dopamine D3 / Q000172:deficiency* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D050637:Receptors, Dopamine D3
keywords: Antigen cross-presentation; Cytotoxic T lymphocytes; Dendritic cells; Dopamine receptors; Knockout mice; Tumor immunology