PI3K/mTOR inhibition induces tumour microenvironment remodelling and sensitises pS6^high uterine leiomyosarcoma to PD-1 blockade.

ABSTRACT:

Background

Uterine leiomyosarcomas (uLMS) are aggressive tumours with poor prognosis and limited treatment options. Although immune checkpoint blockade (ICB) has proven effective in some 'challenging-to-treat' cancers, clinical trials showed that uLMS do not respond to ICB. Emerging evidence suggests that aberrant PI3K/mTOR signalling can drive resistance to ICB. We therefore explored the relevance of the PI3K/mTOR pathway for ICB treatment in uLMS and explored pharmacological inhibition of this pathway to sensitise these tumours to ICB.

Methods

We performed an integrated multiomics analysis based on TCGA data to explore the correlation between PI3K/mTOR dysregulation and immune infiltration in 101 LMS. We assessed response to PI3K/mTOR inhibitors in immunodeficient and huma

SUBMITTER: De Wispelaere W 

PROVIDER: S-EPMC11074386 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature