Research projects

Brain metastases (BM) are the most common tumor of the brain and a devastating complication with unmet therapeutic needs occurring in advanced cancers of the lung, breast and melanoma. Immune checkpoint inhibitors (ICIs) are considered the backbone of systemic therapy for several advanced solid tumors, including non-small cell lung cancer (NSCLC) and melanoma. However, not all patients respond to ICIs and the tumor microenvironment is a crucial determinant of this response. The brain tumour microenvironment (BTME) exhibits particularities when compared to other metastatic niches due to the presence of the glia and microglia. Interestingly, the response to ICIs of intra-cranial lesions differs from the one of extra-cranial lesions indicating that the BTME may preclude the response to ICIs. We have performed a thorough study of BMs from NSCLCs and melanoma compared to their matched primary tumors with a focus in the BTME. We have integrated our findings with the patient clinical response to ICI treatment. This is allowing the identification of novel potential therapeutic targets involved in the response to ICIs of BM patients. These targets are being evaluated and studied through functional models derived from the patients under study such as tumoroids, organotypic cultures and hPDX models. Our study has allowed the identification and validation of therapeutic targets that could lead to novel treatments for NSCLC and melanoma BMs.