Mast-cell derived nerve growth factor drives ILC2 pro-tumoral functions in bladder cancer
- Maryline Falquet
- Hajar El Ahanidi
- Alejandra Gomez-Cadena
- Ziyang Su
- Anthony Cornu
- Tania Wyss
- Burak Kizil
- Robert Pick
- Katayoun Falamaki
- Pratyaksha Wirapati
- Benedetta Fiordi
- Isis Senoner
- Daniela Claudia Maresca
- Neil Kallal
- Danaé Guedj
- Mario Kreutzfeldt
- Jean-Christophe Tille
- Marine M. Leblond
- Katarzyna Michaud
- Silvia Pesce
- Simona Candiani
- Korneliusz Golebski
- Julien Dagher
- Melinda Charrier
- Caroline Pressacco Brossier
- Elisabeth Grobet-Jeandin
- Romina Marone
- Stéphanie Hugues
- Lukas T. Jeker
- Grégory Verdeil
- Doron Merkler
- Emanuela Marcenaro
- Christoph Scheiermann
- Mohammed Attaleb
- Daniel Benamran
- Petros Tsantoulis
- Giuseppe Ercolano
- Sara Trabanelli
- Camilla Jandus
2026-02-21
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.