Nociceptive sensory nerves suppress anti-tumor immunity by blocking tertiary lymphoid structure formation in lung cancer

Summary

This study investigates the role of nociceptive sensory innervation in lung adenocarcinoma (LUAD). The researchers found that LUAD progression amplifies nociceptive sensory neurons, which release the neuropeptide CGRP. CGRP acts on a subset of macrophages, impairing the recruitment of CXCL13+ fibroblasts and blocking the formation of tertiary lymphoid structures (TLS)—a key predictor of LUAD prognosis. Local sensory denervation restores TLS formation and enhances B and T cell anti-tumor immunity. The study identifies CGRP signaling as a druggable, smoking-linked vulnerability that could enhance immunotherapy response in lung cancer preclinical models.

Source

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