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http://hdl.handle.net/2445/175887
Title: | Pharmacological activation of LXR alters the expression profile of tumor-associated macrophages and the abundance of regulatory T cells in the tumor microenvironment |
Author: | Carbó, José M. León Moreno, Theresa Elizabeth Font-Díaz, Joan De la Rosa, Juan Vladimir Castrillo, Antonio Picard, Felix R. Staudenraus, Danel Huber, Magdalena Cedó, Lídia Escolà-Gil, Joan Carles Campos, Lucía Bakiri, Latifa Wagner, Erwin F. Caelles Franch, Carme Stratmann, Thomas Van Ginderachter, J.A. Valledor Fernández, Annabel |
Keywords: | Receptors nuclears (Bioquímica) Càncer Nuclear receptors (Biochemistry) Cancer |
Issue Date: | 23-Dec-2020 |
Publisher: | American Association for Cancer Research |
Abstract: | Liver 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1158/0008-5472.CAN-19-3360 |
It is part of: | Cancer Research, 2020, vol. 81, num. 4 |
URI: | http://hdl.handle.net/2445/175887 |
Related resource: | https://doi.org/10.1158/0008-5472.CAN-19-3360 |
ISSN: | 0008-5472 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) |
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23-12-2021
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