Journal
JCI INSIGHT
Volume 2, Issue 13, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.93179
Keywords
-
Categories
Funding
- NIH [NCI P30 CA014520, R21 AI116007, R21 AI105847, R01 AI069099, R01 CA174462, P01-CA022443]
- NAZ [T32 CA157322]
- University of Wisconsin Carbone Cancer Center
Ask authors/readers for more resources
A central issue for adoptive cellular immunotherapy is overcoming immunosuppressive signals to achieve tumor clearance. While gamma delta 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 delta 2(+) T cells has potent antitumor effects, even in the absence of checkpoint blockade or activating compounds. V delta 2(+) T cell immunotherapy given within the first 5 days of EBV infection almost completely prevented the outgrowth of tumors. V delta 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 delta 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-1(lo) V delta 2(+) T cells circumvent the tumor checkpoint environment in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available