In depth mapping of the neuroblastoma secretome reveals an immunosuppressive secretory phenotype inhibiting effective T cell responses through extracellular vesicles

ABSTRACT: Neuroblastoma is a pediatric solid tumor that remains a challenge for immunotherapy. This limited efficacy is attributed to immunomodulatory factors secreted within the neuroblastoma tumor microenvironment (TME), which suppress T-cell function promoting tumor survival and metastasis. To identify neuroblastoma derived immunomodulatory factors, we isolated and characterized the secretomes of 16 patient-derived tumoroids. These secretomes suppressed T-cell activation, proliferation, and cytotoxicity to varying degrees, demonstrating the presence of factors capable of modulating immune cell function. We therefore profiled the secretomes using LC-MS/MS and identified neuropeptide Y (NPY), together with several previously reported immunomodulatory factors, as significantly enriched in the most suppressive tumoroids. Although neither direct nor indirect effects of NPY on T-cell could be validated, NPY abundance correlated with extracellular vesicle (EV) secretion. This finding suggests that NPY is a biomarker of EV secretion rather than a direct mediator of T-cell suppression and may also indicate the immunosuppressive status of the TME.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Neuroblastoma

SUBMITTER: Elisavet Kalaitsidou  

LAB HEAD: Wei Wu

PROVIDER: PXD082164 | Pride | 2026-08-17

REPOSITORIES: Pride