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

摘要

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.