The diagram shows how sympathetic and parasympathetic nerves, as well as sensory nerves, innervate solid tumors. These nerves release neurotransmitters and neuropeptides, including norepinephrine (NE), acetylcholine (ACh), substance P (SP), and calcitonin gene-related peptide (CGRP). The diagram illustrates the interaction of these neural signals with various cells in the tumor microenvironment, such as endothelial cells, tumor cells, macrophages, CD8 positive T-cells, and fibroblasts. Each cell type expresses specific receptors for these neural signals, which integrate systemic physiological states with local microenvironmental cues. The diagram highlights how these neural inputs coordinate multicellular processes that shape tumor architecture, progression, and treatment response.
Peripheral neural signaling shapes solid tumors. Solid tumors may be innervated by sympathetic and parasympathetic autonomic nerves, as well as sensory nerves. These neurons release neurotransmitters, including norepinephrine (NE, noradrenaline) and acetylcholine (ACh), and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP). Tumor cells and nonmalignant components of the tumor microenvironment, including immune cells, endothelial cells, and fibroblasts, express receptors for these neural signals. Through these cellular targets, neural signaling integrates the systemic physiological state of the individual, including responses to cancer treatment, with local microenvironmental cues such as inflammation. The combined neural inputs coordinate multicellular processes that shape tumor architecture, progression, and treatment response. DAMP, damage-associated molecular pattern; α2AR, α2-adrenergic receptor; β1/2AR, β1/2-adrenergic receptor; M1/3R, M1/3 muscarinic receptor; Ca2+, calcium; MMP, matrix metalloprotease; ECM, extracellular matrix, CLR, calcitonin receptor-like receptor; RAMP1, receptor activity-modifying protein-1.