In J03, Christina Bebber will investigate how neurotransmitter biosynthesis and secretion by small cell lung cancer (SCLC) cells shape the tumor immune microenvironment and contribute to immune evasion. The project will validate ASCL1-selective neurotransmitter secretion in neuroendocrine SCLC and define its impact on T-cell activation, effector function and immunometabolic reprogramming. Using in vitro co-culture systems, metabolomics and immunometabolic assays, it will be characterized how SCLC-derived neurotransmitters and metabolites reprogram tumor-infiltrating immune cells and enforce an immune-cold microenvironment. By integrating functional readouts of T-cell responses with comprehensive metabolic profiling, this project aims to uncover novel metabolic vulnerabilities and signalling axes that can be targeted to enhance the efficacy of immunotherapies in SCLC. The resulting insights into metabolic-immune crosstalk in neuroendocrine SCLC will give new insights into the knowledge gaps in tumor immunometabolism and to inform the rational design of combination strategies that couple metabolic interventions with immune-based therapies.