Adoptively transferred V?9V?2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model.

ABSTRACT: A central issue for adoptive cellular immunotherapy is overcoming immunosuppressive signals to achieve tumor clearance. While ?? 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 V?2+ T cells has potent antitumor effects, even in the absence of checkpoint blockade or activating compounds. V?2+ T cell immunotherapy given within the first 5 days of EBV infection almost completely prevented the outgrowth of tumors. V?2+ 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 V?2+ 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 V?2+ T cells circumvent the tumor checkpoint environment in vivo.

SUBMITTER: Zumwalde NA 

PROVIDER: S-EPMC5499361 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature