@article{oai:nagasaki-u.repo.nii.ac.jp:00026957,
 author = {Nada, Mohanad H. and Wang, Hong and Hussein, Auter J. and Tanaka, Yoshimasa and Morita, Craig T.},
 issue = {1},
 journal = {OncoImmunology},
 month = {Oct},
 note = {Human Vγ2Vδ2 (also termed Vγ9Vδ2) T cells play important roles in microbial and tumor immunity by monitoring foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis. Accumulation of isoprenoid metabolites after bisphosphonate treatment allows Vγ2Vδ2 T cells to recognize and kill tumors independently of their MHC expression or burden of non-synonymous mutations. Clinical trials with more than 400 patients show that adoptive immunotherapy with Vγ2Vδ2 T cells has few side effects but has resulted in only a few partial and complete remissions. Here, we have tested Vγ2Vδ2 T cells for expression of inhibitory receptors and determined whether adding PD-1 checkpoint blockade to adoptively transferred Vγ2Vδ2 T cells enhances immunity to human PC-3 prostate tumors in an NSG mouse model. We find that Vγ2Vδ2 T cells express PD-1, CTLA-4, LAG-3, and TIM-3 inhibitory receptors during the 14-day ex vivo expansion period, and PD-1, LAG-3, and TIM-3 upon subsequent stimulation by pamidronate-treated tumor cells. Expression of PD-L1 on PC-3 prostate cancer cells was increased by co-culture with activated Vγ2Vδ2 T cells. Importantly, anti-PD-1 mAb treatment enhanced Vγ2Vδ2 T cell immunity to PC-3 tumors in immunodeficient NSG mice, reducing tumor volume nearly to zero after 5 weeks. These results demonstrate that PD-1 checkpoint blockade can enhance the effectiveness of adoptive immunotherapy with human γδ T cells in treating prostate tumors in a preclinical model., OncoImmunology, 10(1), art. no. 1989789; 2021},
 title = {PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer},
 volume = {10},
 year = {2021}
}