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Nerve Growth Factor (NGF) drives ILC2 pro-tumoral functions - bulk RNA sequencing of human TRKA+ and TRKA- ILC2s

GSE311046 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/02/06 Platform GPL24676
Summary
ILC2s are key regulators of tissue homeostasis and inflammation. In cancer, ILC2s can exhibit pro-tumoral functions by increasing the MDSC/T-cell ratio. Nevertheless, the upstream ILC2 triggers remain poorly defined. Here, we identify NGF as the driver of ILC2 pro-tumoral functions in bladder cancer patients. We show that ILC2s express the NGF receptor TrkA and respond to NGF by secreting type-2 cytokines. In the tumor microenvironment, NGF-producing mast cells accumulate and activate ILC2s to induce Tregs, ultimately fostering tumor growth. In patients, NGF levels inversely correlate with survival in ILC2-rich tumors, underscoring the clinical significance of this axis. In vivo administration of a selective TrkA inhibitor improves survival in orthotopic tumor-bearing animals and sensitizes them to immune checkpoint blockade (ICB). Overall, we identify NGF as a novel ILC2 activator that shapes pro-tumoral ILC2 functions. The blockade of TrkA+ ILC2s might represent a targetable strategy to improve survival, particularly in ICB-resistant patients.
Published in
Mast-cell derived nerve growth factor drives ILC2 pro-tumoral functions in bladder cancer
Falquet M, El Ahanidi H, Gomez-Cadena A et al. · Nature communications 2026 · PMID 41723132 · doi:10.1038/s41467-026-69841-y
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Also filed as BioProject PRJNA1368597 and SRA study SRP648038. Searching any of these in the dataset finder brings you back here.

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