Neuro-Immune Interaction in Cancer Development

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While the presence of nerves in solid tumors has been observed for hundreds of years, investigation of the impact of these nerves on tumor growth has only been initiated in the last 10 years. The bulk of this work has focused on the impact of neurotransmitters on tumor cell growth and metastasis, however immune cells also express receptors for a wide variety of neurotransmitters, which can have immune-activating and immuneinhibiting properties. In preliminary studies using a murine breast cancer model, we have found that the presence of sensory nerves is necessary for tumor inhibition by the adaptive immune system. Furthermore, blockade of a specific neurotransmitter produced by sensory nerves, calcitonin gene related peptide (CGRP) inhibited tumor growth and improved T cell infiltration into tumors, suggesting both pro- and anti-tumor activities for sensory nerves in breast cancer. In this project, we will decipher how sensory nerves promote adaptive immune responses to tumors. We will also investigate the mechanism by which CGRP inhibition improves tumor control, and whether this treatment can synergize with anti-PD-1 immunotherapy. Finally, we will evaluate whether presence of sensory nerves, adrenergic nerves, or specific neurotransmitters including CGRP correlate with immune infiltration and response to chemotherapy in breast cancer patients. Overall these studies will provide critical information on a potentially novel immunotherapeutic pathway that can be modulated in patients to promote tumor control.