Innate lymphoid cells type 2 (ILC2s) can support tumor growth and survival by increasing the population of myeloid-derived suppressor cells (MDSCs), which inhibit effector T cell mediated anti-tumor immunity. But it is not clear what triggers their pro-tumoral activation. Researchers led by Ludwig Lausanne’s Maryline Falquet and Camilla Jandus reported in a February publication in Nature Communications the nature of that trigger and an additional mechanism by which activated ILC2s induce immunosuppression in the tumor microenvironment in bladder cancer (BC). They showed using patient samples and mouse models that nerve growth factor (NGF) produced by mast cells, which accumulate in the BC tumor microenvironment, activates ILC2s. NGF binding to the high-affinity NGF receptor TrkA, which is specifically expressed by ILC2s, induced IL-5 and IL-13 secretion, a hallmark of ILC2 activation. Maryline, Camilla and colleagues found that activated ILC2s also directly induce the differentiation of naïve CD4+ T cells into regulatory T cells, which sustain their pro-tumoral effects. Further, the researchers demonstrated that an existing inhibitor of the TrkA improves survival in an orthotopic mouse model of BC and sensitizes the mice to checkpoint blockade immunotherapy. In patients, high NGF levels were associated with shorter survival in ILC2-rich bladder tumors, supporting the clinical relevance of these findings and nominating the targeting of TrkA+ ILC2s as a potential immunotherapy for this cancer.
Mast-cell derived nerve growth factor drives ILC2 pro-tumoral functions in bladder cancer
Nature Communications, 2026 February 21