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

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 declin

SUBMITTER: Lauder SN 

PROVIDER: S-EPMC9596434 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature