Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma

Abstract: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear recept...

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Detalles Bibliográficos
Autores principales: Cayrol, María Florencia, Revuelta, Maria V., Debernardi, Maria Mercedes, Paulazo, Maria Alejandra, Phillip, Jude M., Zamponi, Nahuel, Sterle, Helena Andrea, Díaz Flaqué, María Celeste, Magro, Cynthia, Marullo, Rossella, Mulvey, Erin, Ruan, Jia, Cremaschi, Graciela A., Cerchietti, Leandro
Formato: Artículo
Lenguaje:Español
Publicado: American Association for Cancer Research 2022
Materias:
INMUNOLOGIA
LINFOMA DE CÉLULAS T
BEXAROTENO
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/15399
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
Descripción
Sumario:Abstract: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate the aVb3 integrin that is overexpressed in CTCL, potentially interfering the antineoplastic effect of bexarotene. We thus investigated the biological effect of levothyroxine in relation to bexarotene treatment. Although in isolated CTCL cells levothyroxine decreased, in an aVb3-dependent manner, the antineoplastic effect of bexarotene, levothyroxine supplementation in preclinical models was necessary to avoid suppression of lymphoma immunity. Accordingly, selective genetic and pharmacologic inhibition of integrin aVb3 improved the antineoplastic effect of bexarotene plus levothyroxine replacement while maintaining lymphoma immunity. Our results provide a mechanistic rationale for clinical testing of integrin aVb3 inhibitors as part of CTCL regimens based on bexarotene administration.

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