Mast-cell derived nerve growth factor drives ILC2 pro-tumoral functions in bladder cancer

Journal article

Innate lymphoid cells type 2 (ILC2s) are key regulators of tissue homeostasis and inflammation. In cancer, ILC2s can exhibit pro-tumoral functions by increasing the myeloid derived suppressor cells (MDSC)/T-cell ratio. Nevertheless, the upstream ILC2 triggers remain poorly defined. Here, we identify nerve growth factor (NGF) as the driver of ILC2 pro-tumoral functions in patients with bladder cancer. 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 regulatory T cells (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 female mice and sensitizes them to immune checkpoint blockade (ICB). Overall, we identify NGF as an 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.

Authors: Falquet, M; El Ahanidi, H; Gomez-Cadena, A; Su, Z; Cornu, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 17
• Issue: 1
• Article number: 3061
• Publication date: 2026-02-21
• Acceptance date: 2026-02-11
• DOI: 10.1038/s41467-026-69841-y
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Innate lymphoid cell; Blockade; Nerve growth factor; Interleukin 33; Bladder cancer; Immune system; Receptor; Tropomyosin receptor kinase A; Suppressor