The increased IL-17-producing γδT cells promote tumor cell proliferation and migration in neuroblastoma

Neuroblastoma (NB) is the most common solid extracranial malignancy in children with a considerable chance of metastatic progression. Prevalent evidence supports the anti-tumor role of gamma delta T cells and these cells have been testing in clinical trials for constraining tumor growth. A small subpopulation of gamma delta T cells releasing IL-17, however, were demonstrated to exert tumor-promoting effects in many aspects. In this study, we found an augment of IL-17 + gamma delta T cells both in in vitro PAM-stimulated gamma delta T-cell expanding culture and circulating gamma delta T cells in NB patients. These patient-origin cells expanded in vitro by PAM in the presence of IL-17 polarizing condition were shown to promote the proliferation and migration of NB cells. Furthermore, an intrinsic preference for IL-17 polarization in NB gamma delta T cells was revealed by mRNA microarray and Western Blot, which pointed to an up-regulated expression of multiple Th17-development related genes in addition to an increased phosphorylation level of STAT3.