γδ T cells are the prime antitumoral T cells in pediatric neuroblastoma

Abstract

High-risk pediatric neuroblastoma patients have a dismal survival rate despite intensive treatment regimens. New treatment options are thus required. Even though HLA expression in neuroblastoma is low and immune cell infiltrates are limited, the presence of tumor-infiltrating lymphocytes (TILs) is indicative of better patient survival. Here, we show that most tumor lesions contain viable immune cell infiltrates after induction chemotherapy, with high percentages of CD3+ T cells. We therefore expanded the TILs and tested their antitumoral activity. With sufficient starting material, TIL expansion was as efficient as for adult solid tumors. However, whereas TIL products from adult tumors almost exclusively contained αβ T cells, in neuroblastoma-derived TIL products, γδ T cells expanded with similar efficacy as αβ T cells. Importantly, the antitumor responses in response to autologous tumor digest primarily originated from (Vδ1- and Vδ3-expressing) γδ T cells, and not from αβ T cells. In conclusion, this finding creates a window of opportunity for immunotherapy for neuroblastoma patients, with γδ T cells as potential prime responders.