Details

Autor(en) / Beteiligte

• Almeida‐Santos, José
• Bergman, Marie‐Louise
• Amendoeira Cabral, Inês
• Correia, Vasco
• Caramalho, Íris
• Demengeot, Jocelyne

Titel

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

Ist Teil von

• European journal of immunology, 2020-03, Vol.50 (3), p.439-444

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. Genetic alterations at the Foxp3 locus are most commonly associated with autoimmunity and inflammatory manifestations. In this work we evidence that a Foxp3 variant known to affect regulatory T cell functions acts as an hypomorph in a tumor context and enhances the effectiveness of anti‐CTLA4 immunotherapy.