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  5. Unveiling the role of FoxP3 splicing variants in regulatory T cells (Tregs) from subjects with breast cancer (DSB.AD001.080)
Research project

Unveiling the role of FoxP3 splicing variants in regulatory T cells (Tregs) from subjects with breast cancer (DSB.AD001.080)

Thematic area

Biomedical sciences

Project area

Oncologia e Immunologia (DSB.AD001)

Structure responsible for the research project

Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS)

Project manager

VERONICA DE ROSA
Phone number: 0817463058
Email: veronica.derosa@cnr.it

Abstract

CD4+CD25highFoxP3+ regulatory T cells (Tregs), are central players in the prevention of autoimmune diseases, allergy, and
fetal-maternal tolerance but, as a double-edged sword, FoxP3+ Tregs can also suppress anti-tumor immune responses and favor
tumor progression. For these reasons, FoxP3+ Tregs represent a primary target for cancer immunotherapy, which finally aims at
restoring the ability of the immune system to detect and destroy cancer cells. The tumor microenvironment has been reported to
contain a "rich milieu" of molecules capable of increasing the conversion of naïve CD4+ T cells into FoxP3+ Tregs, the
recruitment of peripheral FoxP3+ Tregs to the tumor site and their expansion. Compelling experimental evidence has shown an
increased percentage of FoxP3+ Tregs in the peripheral blood and in the tumor microenvironment of subjects with different
tumors, including breast cancer (BC). Moreover, their abundant presence in tumor infiltrates leads to reduced survival in cancer
subjects and inversely correlates with clinical response of BC to therapy.

Goals

Our idea is to evaluate whether increased immunosuppression, observed in tumor-affected subjects, could be secondary to the
induction of FoxP3E2+ Tregs, characterized by a stronger suppressive capacity, due to the engagement of specific metabolic
programs. Starting from these observations, we plan to evaluate whether women with BC have increased expression of FoxP3E2
in Tregs when compared with normal individuals. The analysis of the specific metabolic pathways (i.e. glycolysis or fatty acids
oxidation) responsible for the induction of Tregs phenotype and specific FoxP3 splicing variants in BC, will be also evaluated.
Our approach should permit the selection of BC tumors with FoxP3E2+ Tregs, possibly relevant for both a better prognostic
assessment and the selection of the more suitable therapeutic regime soon after diagnosis of BC.

Start date of activity

02/01/2016

Keywords

Treg, Breast cancer, FoxP3

Last update: 30/04/2024