Fusco, Clorinda (2021) Preferential accumulation of Foxp3E2+ regulatory T cells with highly immunosuppressive phenotype in breast cancer subjects. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Preferential accumulation of Foxp3E2+ regulatory T cells with highly immunosuppressive phenotype in breast cancer subjects
Creators:
CreatorsEmail
Fusco, Clorindaclorinda.fusco@unina.it
Date: 14 July 2021
Number of Pages: 57
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Dottorato: Medicina molecolare e biotecnologie mediche
Ciclo di dottorato: 33
Coordinatore del Corso di dottorato:
nomeemail
Santoro, Massimomasantor@unina.it
Tutor:
nomeemail
Matarese, GiuseppeUNSPECIFIED
Date: 14 July 2021
Number of Pages: 57
Keywords: Breast cancer, Treg cells, Foxp3E2+ cells.
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 19 Jul 2021 11:04
Last Modified: 07 Jun 2023 11:25
URI: http://www.fedoa.unina.it/id/eprint/13818

Collection description

Regulatory T CD4+Foxp3+ (Treg) cells are a cellular subset involved in the maintenance of immune self-tolerance and homeostasis but, as a double-edged sword, they can also suppress anti-tumor immune response and favor tumor progression. Therefore, Foxp3+ Treg cells 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 able to increase the recruitment of Foxp3+ Treg cells to the tumor site. Compelling experimental evidence has shown an increased percentage of Foxp3+ Treg cells 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. The transcription factor Foxp3 plays a critical role in regulating the development and the immunosuppressive function of Treg cells and up to 8 different Foxp3 splicing variants have been described in human subjects, but their role and function still remain elusive. Recently, it has been found that among all the different Foxp3 splicing forms, those containing the exon2 (Foxp3E2) are necessary for the induction and establishment of the suppressive phenotype of Treg cells. The aim of this thesis was to evaluate the role of Foxp3E2+ Treg cells in the context of tumor growth, dissecting whether increased immunosuppression observed in BC subjects, could be secondary to the preferential accumulation of Foxp3E2+ Treg cells. In conclusion, the evaluation of the number of Foxp3E2+ Treg cells in BC tumors could represent a prognostic assay for the assessment of tumor progression, severity and prognosis. In addition, Foxp3E2+ Treg cells could be pharmacological targeted in order to inhibit their immunosuppressive activity in the tumor microenvironment, thus sustaining anti-tumor immune response and reducing tumor progression.

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