Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer with a global annual incidence of around 250,000 cases and a five-year survival rate of less than 10 %. Immunosuppressive and tumor-promoting M2 macrophages are prominent in the SCLC tumor microenvironment (TME) and have been linked to increased metastasis. Additionally, a low infiltration by cytotoxic CD8⁺ T cells and the presence of immunosuppressive regulatory T lymphocytes counteract tumor-suppressive immune system activation.

Neurotransmitters have been established as signaling molecules that modulate the functions of various immune cell types and play a role in modulating cancer immunity in the TME. Our preliminary data suggests that SCLC tumor cells are able to produce the neurotransmitters GABA and serotonin. The aim of this project is to explore the SCLC-to-immune cell communication employing these neurotransmitters. We hypothesize that GABA and serotonin are produced by SCLC tumor cells and released into the TME in order to suppress anti-tumor immune functions and create a pro-tumor environment, contributing to its pathology. Specifically, we focus on the effects of GABA and serotonin on CD8⁺ T cells and tumor associated macrophages.

https://www.translational-genomics.de/research-groups/beleggia-lab