WP 1: Immune-PET and lung cancer

Development of novel Immuno-PET tracers for in vivo imaging of tumor-associated immunity

Despite the demonstrated effectiveness of immunoregulatory agents such as immune checkpoint blockers (ICB) on refractory cancers, these therapies work satisfactorily only in a reduced subset of patients. Further, ICB treatments are not exempt of risks and are associated to very high costs. Reliable response biomarkers are needed to identify responders and non-responders, and conventional imaging modalities and/or wet biomarkers have not proved adequate. Recently, the immune contexture of the tumor microenvironment was introduced as a new concept that classifies tumors by quantifying immune cell densities and other immune markers, and defines the chances for responding to immunotherapy. For the case of PD-1/PD-L1 inhibitors, patients are currently stratified by determining tumor expression of the target molecules from a biopsy collected prior treatment. However, the procedure is invasive, introduces risks of tumor cells dissemination and is associated with low sensitivity and specificity due to intratumoral heterogeneity.

Positron emission tomography (PET) is a powerful, quantitative, non-invasive imaging technique that permits longitudinal analyses of biological processes in vivo by administration of a radiolabeled probe. In this project we aim at exploiting PET technology for doing spatial and temporal tracking of intratumoral T lymphocytes and other relevant immune-markers to stratify patients amenable for immunotherapy, and to monitor responses to therapeutic interventions.