The impact of sensory neurons on tumor burden and immune response in NSCLC 2260151

Abstract

Abstract Introduction Non-small cell lung cancer (NSCLC) is a malignancy of the epithelial cells in the lung originating from the central bronchi spreading to the terminal alveoli. It is the most common form, accounting for 85% of diagnoses. The low 5-year survival rate of 28% is due to acquired treatment resistance to standard of care anti PD-L1 immunotherapy. Therefore, it is pertinent to understand NSCLC immune signaling and fully describe cellular niches within the tumor microenvironment. Sensory neurons of the peripheral nervous system (PNS) have been shown to modulate immune responses across cancer types. Increased innervation and neuropeptide secretion is associated with increased tumor burden and dysregulated immune cell function. Neuropeptide substance P (SP) has been shown to drive breast cancer metastasis, and sensory neurons contribute to regulating immune responses in allergies, homeostasis, and infection. Methods In a tumor injectable mouse model of NSCLC with KRAS and p53 mutations (KP), lung tissue was broad cell immunophenotyped, and immunofluorescently stained with neuronal, immune, and tumoral markers. Cell supernatant was used for neuropeptide ELISA and cytokine analysis. This was performed in C57BL/6 and Tac1KO mice. Results SP immunofluorescence staining and ELISA showed increased expression in KP injected mice compared to control. When the SP-encoding gene Tac1 is knocked out, tumor burden is increased. We hypothesize this is due to dysregulated immune cell populations, particularly macrophages. Conclusion To approach NSCLC from a new perspective, we probe the impact of sensory neurons and neuropeptides on immune response and tumor burden in a KP tumor injectable mouse model, where we knockout neuropeptide SP. To better understand potential mechanism and neuron induced modulation of the tumor microenvironment, we plan to investigate neuropeptide level expression and immunophenotyping within the tumor injectable mouse model, human patient samples, and human co-culture in vitro models of NSCLC. Funding Source R01HL165259-01A, R01HL165259-03S2 Topic Categories Neuroimmunology (NEUR)