Diminished cytolytic activity of γδ T cells with reduced DNAM-1 expression in neuroblastoma patients

Neuroblastoma is one of the children's malignant tumors with poor prognosis, as well as high recurrence and metastasis rates after surgical removal and chemotherapy. gamma delta T-cell based immunotherapy receives increasing attention thanks to the strong cytolytic activity to tumor cells. Our previous data revealed a significant increase in circulating gamma delta T-cell frequency in NB patients. In the present study, we found that beside a reduction of IFN-gamma in serum of NB patients, DNAM-1 expression decreased in both circulating and PAM-expanded NB gamma delta T cells. Upon PAM stimulation, NB gamma delta T cells showed a reduced level of cell proliferation. In addition, the cytolytic activity of NB gamma delta T cells to NB cell lines was proved to be attenuated in a co-culture system. The fact that DNAM-1 neutralizing antibody abolished the tumor cell killing accentuates the indispensable role of DNAM-1 molecule in gamma delta T-cell cytolytic function.