Understanding how tumour cells communicate with their surroundings is a major challenge in cancer biology and could explain why some cancers grow quickly or fail to respond well to therapy. This PhD project will explore how cancers with hyperactive mTORC1 signalling interact with their microenvironment and the immune system, with a particular focus on extracellular vesicles (EVs) as mediators of signalling.

mTORC1 is frequently overactivated in cancers of the kidney, prostate and lung. Emerging evidence suggests that mTORC1‑active tumour cells can reshape the tumour microenvironment, but the mechanisms driving this remain poorly understood. Although inhibitors of this pathway are widely used, their clinical benefit as single agents has been limited.

What will you investigate?

In this project, you will use patient‑derived TSC2‑deficient cell models to investigate how mTORC1‑active cells influence inflammation and immunity through their secreted factors. You will characterise both soluble proteins and EV‑associated cargo using proteomics and existing RNA datasets, allowing you to identify key immune‑modulatory signals released by mTORC1-active cells.

Given reports of reduced T‑cell infiltration in mTORC1‑active tumours, you will test the hypothesis that tumour‑derived EVs suppress T‑cell activation. You will examine whether exposure to EVs alters T‑cell transcriptional responses and functional activation, providing mechanistic insight into tumour‑induced immune suppression.

Understanding how tumour cells communicate with their surroundings is a major challenge in cancer biology and could explain why some cancers grow quickly or fail to respond well to therapy. This PhD project will explore how cancers with hyperactive mTORC1 signalling interact with their microenvironment and the immune system, with a particular focus on extracellular vesicles (EVs) as mediators of signalling.

mTORC1 is frequently overactivated in cancers of the kidney, prostate and lung. Emerging evidence suggests that mTORC1‑active tumour cells can reshape the tumour microenvironment, but the mechanisms driving this remain poorly understood. Although inhibitors of this pathway are widely used, their clinical benefit as single agents has been limited.

What will you investigate?

In this project, you will use patient‑derived TSC2‑deficient cell models to investigate how mTORC1‑active cells influence inflammation and immunity through their secreted factors. You will characterise both soluble proteins and EV‑associated cargo using proteomics and existing RNA datasets, allowing you to identify key immune‑modulatory signals released by mTORC1-active cells.

Given reports of reduced T‑cell infiltration in mTORC1‑active tumours, you will test the hypothesis that tumour‑derived EVs suppress T‑cell activation. You will examine whether exposure to EVs alters T‑cell transcriptional responses and functional activation, providing mechanistic insight into tumour‑induced immune suppression.