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dc.contributor.authorCarbó, José M.-
dc.contributor.authorLeón Moreno, Theresa Elizabeth-
dc.contributor.authorFont-Díaz, Joan-
dc.contributor.authorDe la Rosa, Juan Vladimir-
dc.contributor.authorCastrillo, Antonio-
dc.contributor.authorPicard, Felix R.-
dc.contributor.authorStaudenraus, Danel-
dc.contributor.authorHuber, Magdalena-
dc.contributor.authorCedó Giné, Lídia-
dc.contributor.authorEscolà-Gil, Joan Carles-
dc.contributor.authorCampos, Lucía-
dc.contributor.authorBakiri, Latifa-
dc.contributor.authorWagner, Erwin F.-
dc.contributor.authorCaelles Franch, Carme-
dc.contributor.authorStratmann, Thomas-
dc.contributor.authorVan Ginderachter, J.A.-
dc.contributor.authorValledor Fernández, Annabel-
dc.description.abstractLiver X receptors (LXR) are transcription factors from the nuclear receptor family that are activated by oxysterols and synthetic high-affinity agonists. In this study, we assessed the anti-tumor effects of synthetic LXR agonist TO901317 in a murine model of syngeneic Lewis Lung carcinoma. Treatment with TO901317 inhibited tumor growth in wild-type but not in LXR-deficient mice, indicating that the anti-tumor effects of the agonist depends on functional LXR activity in host cells. Pharmacological activation of the LXR pathway reduced the intratumoral abundance of regulatory T cells (Treg) and the expression of the Treg-attracting chemokine Ccl17 by MHCIIhigh tumor-associated macrophages (TAM). Moreover, gene expression profiling indicated a broad negative impact of the LXR agonist on other mechanisms used by TAM for the maintenance of an immunosuppressive environment. In studies exploring the macrophage response to GM-CSF or IL-4, activated LXR repressed IRF4 expression, resulting in subsequent downregulation of IRF4-dependent genes including Ccl17. Taken together, this work reveals the combined actions of the LXR pathway in the control of TAM responses that contribute to the anti-tumoral effects of pharmacological LXR activation. Moreover, these data provide new insights for the development of novel therapeutic options for the treatment of cancer.-
dc.format.extent19 p.-
dc.publisherAmerican Association for Cancer Research-
dc.relation.isformatofVersió postprint del document publicat a:
dc.relation.ispartofCancer Research, 2020, vol. 81, num. 4-
dc.rights(c) American Association for Cancer Research, 2020-
dc.subject.classificationReceptors nuclears (Bioquímica)-
dc.subject.otherNuclear receptors (Biochemistry)-
dc.titlePharmacological activation of LXR alters the expression profile of tumor-associated macrophages and the abundance of regulatory T cells in the tumor microenvironment-
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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