Differential effects of inhibitors of the PI3K/mTOR pathway on the expansion and functionality of regulatory T cells

Differential effects of inhibitors of the PI3K/mTOR pathway on the expansion and functionality of regulatory T cells

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 168(2016) vom: 18. Juli, Seite 47-54
1. Verfasser: Huijts, Charlotte M (VerfasserIn)
Weitere Verfasser: Santegoets, Saskia J, Quiles Del Rey, Maria, de Haas, Richard R, Verheul, Henk M, de Gruijl, Tanja D, van der Vliet, Hans J
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't PI3K Rapamycin Treg mTOR Aminopyridines Antineoplastic Agents Cytokines Imidazoles mehr... Morpholines NVP-BKM120 Phosphoinositide-3 Kinase Inhibitors Quinolines Everolimus 9HW64Q8G6G MTOR protein, human EC 2.7.1.1 TOR Serine-Threonine Kinases EC 2.7.11.1 dactolisib RUJ6Z9Y0DT Sirolimus W36ZG6FT64
Beschreibung
Zusammenfassung:Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
The PI3K/mTOR pathway is commonly deregulated in cancer. mTOR inhibitors are registered for the treatment of several solid tumors and novel inhibitors are explored clinically. Notably, this pathway also plays an important role in immunoregulation. While mTOR inhibitors block cell cycle progression of conventional T cells (Tconv), they also result in the expansion of CD4(+)CD25(hi)FOXP3(+) regulatory T cells (Tregs), and this likely limits their clinical antitumor efficacy. Here, we compared the effects of dual mTOR/PI3K inhibition (using BEZ235) to single PI3K (using BKM120) or mTOR inhibition (using rapamycin and everolimus) on Treg expansion and functionality. Whereas rapamycin, everolimus and BEZ235 effected a relative expansion benefit for Tregs and increased their overall suppressive activity, BKM120 allowed for similar expansion rates of Tregs and Tconv without altering their overall suppressive activity. Therefore, PI3K inhibition alone might offer antitumor efficacy without the detrimental selective expansion of Tregs associated with mTOR inhibition
Beschreibung:Date Completed 30.03.2017
Date Revised 04.12.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2016.05.005