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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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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
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author Almeida‐Santos, José
Bergman, Marie‐Louise
Amendoeira Cabral, Inês
Correia, Vasco
Caramalho, Íris
Demengeot, Jocelyne
author_facet Almeida‐Santos, José
Bergman, Marie‐Louise
Amendoeira Cabral, Inês
Correia, Vasco
Caramalho, Íris
Demengeot, Jocelyne
author_sort Almeida‐Santos, José
collection PubMed
description 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.
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spelling pubmed-70788712020-03-19 The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice Almeida‐Santos, José Bergman, Marie‐Louise Amendoeira Cabral, Inês Correia, Vasco Caramalho, Íris Demengeot, Jocelyne Eur J Immunol Tumor immunology 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. John Wiley and Sons Inc. 2019-11-27 2020-03 /pmc/articles/PMC7078871/ /pubmed/31729760 http://dx.doi.org/10.1002/eji.201948251 Text en © 2019 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Tumor immunology
Almeida‐Santos, José
Bergman, Marie‐Louise
Amendoeira Cabral, Inês
Correia, Vasco
Caramalho, Íris
Demengeot, Jocelyne
The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
title The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
title_full The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
title_fullStr The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
title_full_unstemmed The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
title_short The multifaceted Foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
title_sort multifaceted foxp3(fgfp) allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
topic Tumor immunology
url 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
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