@article{10.1172/jci.insight.93179, author = {Nicholas A. Zumwalde AND Akshat Sharma AND Xuequn Xu AND Shidong Ma AND Christine L. Schneider AND James C. Romero-Masters AND Amy W. Hudson AND Annette Gendron-Fitzpatrick AND Shannon C. Kenney AND Jenny E. Gumperz}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Adoptively transferred Vγ9Vδ2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model}, year = {2017}, month = {7}, volume = {2}, url = {https://insight.jci.org/articles/view/93179}, abstract = {A central issue for adoptive cellular immunotherapy is overcoming immunosuppressive signals to achieve tumor clearance. While γδ T cells are known to be potent cytolytic effectors that can kill a variety of cancers, it is not clear whether they are inhibited by suppressive ligands expressed in tumor microenvironments. Here, we have used a powerful preclinical model where EBV infection drives the de novo generation of human B cell lymphomas in vivo, and autologous T lymphocytes are held in check by PD-1/CTLA-4–mediated inhibition. We show that a single dose of adoptively transferred Vδ2+ T cells has potent antitumor effects, even in the absence of checkpoint blockade or activating compounds. Vδ2+ T cell immunotherapy given within the first 5 days of EBV infection almost completely prevented the outgrowth of tumors. Vδ2+ T cell immunotherapy given more than 3 weeks after infection (after neoplastic transformation is evident) resulted in a dramatic reduction in tumor burden. The immunotherapeutic Vδ2+ T cells maintained low cell surface expression of PD-1 in vivo, and their recruitment to tumors was followed by a decrease in B cells expressing PD-L1 and PD-L2 inhibitory ligands. These results suggest that adoptively transferred PD-1lo Vδ2+ T cells circumvent the tumor checkpoint environment in vivo.}, number = {13}, doi = {10.1172/jci.insight.93179}, url = {https://doi.org/10.1172/jci.insight.93179}, }