Molecular basis of the contribution of a common AIRE allelic variant to the targeting of organ-specific autoimmunity and quality of anti-tumor responses

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The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice

Publication . Almeida-Santos, Jose; Bergman, Marie-Louise; Jocelyne, Demengeot; Correia, Vasco; Caramalho, Iris; Cabral, Ines

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 Foxp3fgfp 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 Foxp3fgfp 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.

2019-11-15Journal article

Open access