Sensory and autonomic innervation of the tumor-draining lymph nodes limit protective anti-tumor immune response.

Summary: Abstract Body: Sensory and autonomic nervous systems are critical regulators of cancer progression, acting by direct nerve-cancer interaction as well as via indirect modulation of protective immune responses. The neuro-immune control of cancer progression has been largely investigated by employing either global, whole body, or locoregional surgical, chemical or genetic denervation or gene deletion methods. These approaches are unable to fully capture organ-specific influences of nerves on immunosurveillance. This is particularly true for secondary lymphoid organs, which are critical sites for antigen-driven selection and amplification of protective anti-tumor immunity. Tumor-draining lymph nodes (TDLNs) carry broad clinical significance, acting as the front line for immune response activation and a condiut for malignant cell spread. TDLNs are frequently surgically accessed for cancer staging, determination of prognosis and guidance of therapy. We discovered that selective inhibition of either afferent (sensory) or sympathetic innervation of melanoma TDLNs significantly slowed tumor growth in mouse models. Ablating TDLN innervation also improved protective immune responses to melanoma, characterized by diminished tumor-associated TDLN remodeling, improved cell trafficking and antigen-specific cellular immunity. Our results illustrate that targeting TDLN innervation may provide therapeutic benefit, especially if employed as an immunotherapy adjuvant. Kunal Singh¹, Natalie Murray¹, Yuri Bunimovich^{1, 2, 3} 1. Dermatology, University of Pittsburgh, Pittsburgh, PA, United States. 2. Immunology, University of Pittsburgh, Pittsburgh, PA, United States. 3. UPMC Hillman Cancer Center, Pittsburgh, PA, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance