In this workpackage we will explore novel strategies to harness the immune system to fight cancers. Relevant murine models of induced melanoma or transplanted lung cancer will be used as preclinical platforms for the evaluation of clinically relevant immunotherapeutic approaches.
Approaches aimed at better exploiting the innate immune system to develop immunotherapeutic approaches will be evaluated, including the evaluation of the antigen-presenting machinery of tumour antigens and the possibility to develop mRNA-based vaccination protocols against well-established tumour antigens. Finally, the possibility to exploit a subset of T cells with innate-like characteristics (the gd TcR-expressing cells) will be evaluated. The ability of these cells to home to selected peripheral tissues, their propensity to differentiate by default toward a cytotoxic/inflammatory effector cell and their lack of MHC restriction render this cell population an attractive target for guided immunotherapy.
Building upon recent work performed within our consortium both in human and mouse models, we will undertake the identification of the molecular target recognized on several tumour cell lines by a subset of gd T cells recently identified within our consortium, and by analysing the anti-melanoma potential of skin resident gd T cells.