Grant: Project Grant

Triple-negative breast cancer (TNBC), accounting for 15 to 20% of all breast cancers, is associated with earlier age onset, therapeutic resistance, metastasis, and lower survival rates. Immunotherapy, in which the patient's immune system is reprogrammed to attack tumour cells and fight the disease, has improved the outcome of poor-prognosis cancers. In TNBC, immunotherapy targeting a protein called PD-L1 has been approved in combination with chemotherapy. However, only 20% of TNBC express PD-L1 and the clinical benefit remains to be established. Novel therapeutic options are therefore urgently needed for such non-responsive patients. Other proteins from the family of PD-L1 are also involved in the regulation of the immune system in cancers but have been far less studied. Among them, one protein called B7-H4 represents a valuable novel therapeutic target in TNBC. This project builds on our preliminary data demonstrating that B7-H4 is highly present in tumours where PD-L1 is absent and is required for tumour growth and infiltration of immune cells. We will validate B7-H4 as a viable therapeutic target for non-responsive and poor- outcome TNBCs. We developed molecules attached directly to nucleic acids (DNA or RNA) that improve their distribution in the body and increase their activity. In this project, we will use this technology to decrease the amount of B7-H4 in TNBC cells and confirm its potential as a therapeutic target. B7-H4 is not only involved in breast, but in a wide variety of cancers. This project brings together the expertise of chemistry and cancer biology labs and aims to yield new therapeutic options to treat aggressive cancers, with the potential to greatly improve the lives of patients.