PI: Landi Lorenza.
Other IRE Principal Collaborators: Nisticò Paola, Di Modugno Damiani Francesca Romana, Blandino Giovanni, Minuti Gabriele, Porciello Nicla, Baldari Silvia

Project duration: 24 months

Project code: PNRR-MCNT1-2023-12377772

The project, titled "Immune Metabolism Dysregulation and Efficacy of Anti-PD-1/PD-L1 Agents in Non-Small Cell Lung Cancer (NSCLC)", investigates the role of metabolic dysregulation in the tumor microenvironment (TME) and its impact on immunotherapy outcomes. Specifically, the project focuses on the metabolic rewiring of tumor cells, immune cells, and cancer-associated fibroblasts in NSCLC patients treated with immune checkpoint inhibitors (ICIs). By leveraging advanced technologies, such as digital spatial profiling and ex vivo models like tissue slices and patient-derived organoids, the study aims to identify metabolic signatures linked to therapy response.

The primary objective is to discover and validate metabolic biomarkers that can predict sensitivity or resistance to ICIs in NSCLC patients, thereby improving patient selection and treatment strategies. A secondary goal is to explore novel metabolic pathways as potential therapeutic targets, enhancing the efficacy of immunotherapy in both advanced and early-stage settings.

The project is expected to deliver a comprehensive understanding of how metabolism in the TME influences the success of ICIs. Key outcomes include the identification of metabolic signatures correlating with clinical and pathological responses, improved biomarker-driven patient stratification, and the validation of new therapeutic approaches targeting metabolism to restore favorable immune responses. This will ultimately contribute to better prediction of treatment efficacy and the development of novel combination therapies in NSCLC.