Targeting oncogenic hubs of solid tumours to overcome immune evasion from adoptive T cell transfer

Project Summary

We focus on CAR-T and gd T cells that recognise and kill tumour cells independently of the major histocompatibility complex (MHC) to overcome some of the major mechanisms by which tumours avoid MHC-restricted T cell recognition. We will decipher whether oncogenic signalling downstream of oncogenic PI3K or BRAF (i) regulates ECM stiffness, which in turn reduces tumour infiltration by adoptively transferred T cells; (ii) enhances the recognition and elimination of tumour cells by human gd T cells and (iii) drives expression of PD-L1 and its impact on adoptive cell transfer using novel CAR-T designs or gd T cells.