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The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice

It is well established that therapeutic impairment of Foxp3(+) Treg in mice and humans favors immune rejection of solid tumors. Less explored is the impact Foxp3 allelic variants may have on tumor incidence, progression and therapy. In this work, we tested and demonstrate that the Foxp3(fgfp) report...

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Detalles Bibliográficos
Autores principales: Almeida‐Santos, José, Bergman, Marie‐Louise, Amendoeira Cabral, Inês, Correia, Vasco, Caramalho, Íris, Demengeot, Jocelyne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078871/
https://www.ncbi.nlm.nih.gov/pubmed/31729760
http://dx.doi.org/10.1002/eji.201948251
Descripción
Sumario:It is well established that therapeutic impairment of Foxp3(+) Treg in mice and humans favors immune rejection of solid tumors. Less explored is the impact Foxp3 allelic variants may have on tumor incidence, progression and therapy. In this work, we tested and demonstrate that the Foxp3(fgfp) reporter allele, found previously to either enhance or reduce Treg function in specific autoimmunity settings, confers increased anti‐tumor immunity. Our conclusions stem out of the analysis of three tumor models of different tissue origin, in two murine genetic backgrounds. When compared to wild type animals, mice carrying the Foxp3(fgfp) allele spontaneously delay, reduce or prevent primary tumor growth, decrease metastasis growth, and potentiate the response to anti‐CTLA4 monotherapy. These findings suggest allelic variances at the Foxp3 locus may serve as predictive indicators for personalized therapy and prognostics, and point at possible new therapeutic targets.