Adoptively transferred Vγ9Vδ2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model

• Published in: JCI insight Vol. 2; no. 13
• Main Authors: Zumwalde, Nicholas A, Sharma, Akshat, Xu, Xuequn, Ma, Shidong, Schneider, Christine L, Romero-Masters, James C, Hudson, Amy W, Gendron-Fitzpatrick, Annette, Kenney, Shannon C, Gumperz, Jenny E
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 06.07.2017
• Subjects: Oncology; Immunology
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.93179

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.