Targeting of Tripartite Neuron-Cancer-Immune Cell Crosstalk Augments Response to Chemotherapy and Immunotherapy

While there are extensive reports on sympathetic nerve fibers, effect of parasympathetic neurons on cancer progression and immunosuppression still remains elusive. In colorectal cancer tissues, we observed presence of cholinergic parasympathetic nerve fibers near tumor stroma and elevated acetylcholine levels as compared to adjacent normal.

To disrupt this crosstalk, we used Bupivacaine (BUP), an FDA-approved local anesthetic, delivered via a hydrogel (BUP-Gel) for localized release. BUP-Gel inhibited tumor growth across multiple murine models. Further, single cell RNA analysis revealed reshaping of TME, enhancing M1-like macrophages and cytotoxic T-cell activation.