UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Treg-driven tumour control by PI3Kδ inhibition limits myeloid-derived suppressor cell expansion

Lauder, Sarah N; Smart, Kathryn; Bart, Valentina MT; Pires, Ana; Scott, Jake; Milutinovic, Stefan; Godkin, Andrew; ... Gallimore, Awen; + view all (2022) Treg-driven tumour control by PI3Kδ inhibition limits myeloid-derived suppressor cell expansion. British Journal of Cancer 10.1038/s41416-022-01917-0. (In press). Green open access

[thumbnail of s41416-022-01917-0.pdf]
Preview
Text
s41416-022-01917-0.pdf - Published Version

Download (616kB) | Preview

Abstract

BACKGROUND: Recent studies have demonstrated that blocking the PI3Kδ signalling enzyme (by administering a small molecule inhibitor, PI-3065) can potently improve the anti-tumour T-cell response through direct inhibition of Tregs. This treatment also has a negative impact on MDSC numbers but the primary mechanism driving this effect has remained unclear. METHODS: The 4T1 breast cancer mouse model was used in combination with PI-3065 to gain insights into the effect of PI3Kδ inhibition on MDSCs. RESULTS: PI-3065 treatment resulted in a concomitant reduction in MDSC expansion and tumour size. However, targeting Tregs independent of PI-3065 was also associated with reduced tumour volume and MDSC numbers. Surgical removal of tumours resulted in a rapid and significant decline in MDSC numbers, whilst ex vivo studies using cells from PI-3065-treated mice demonstrated no direct effect of the inhibitor on MDSC activity. CONCLUSIONS: Our data suggest that MDSCs are not inhibited directly by PI-3065 treatment but that their reduced recruitment and immunosuppression within the tumour microenvironment is an indirect consequence of PI3Kδ-inhibition-driven tumour control. This indicates that PI3Kδ inhibition drives tumour immunity by breaking down multiple immunosuppressive pathways through both direct mechanisms (on Treg) and indirect mechanisms, secondary to tumour control (on MDSCs).

Type: Article
Title: Treg-driven tumour control by PI3Kδ inhibition limits myeloid-derived suppressor cell expansion
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41416-022-01917-0
Publisher version: https://doi.org/10.1038/s41416-022-01917-0
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Tumour immunology
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10154235
Downloads since deposit
11Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item