%0 Journal Article %J Blood %D 2010 %T Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. %A Zhou, Qing %A Munger, Meghan E %A Highfill, Steven L %A Tolar, Jakub %A Weigel, Brenda J %A Riddle, Megan %A Sharpe, Arlene H %A Vallera, Daniel A %A Azuma, Miyuki %A Levine, Bruce L %A June, Carl H %A Murphy, William J %A Munn, David H %A Blazar, Bruce R %K Animals %K Antibodies, Monoclonal %K Antigens, CD274 %K Antigens, CD8 %K Antigens, CD80 %K Antigens, Surface %K Apoptosis Regulatory Proteins %K Gene Expression Regulation, Leukemic %K Leukemia, Myeloid, Acute %K Lymphocyte Depletion %K Membrane Glycoproteins %K Mice %K Mice, Inbred C57BL %K Mice, Knockout %K Peptides %K Programmed Cell Death 1 Receptor %K T-Lymphocytes, Cytotoxic %K T-Lymphocytes, Regulatory %X Tumor-induced immune defects can weaken host immune response and permit tumor cell growth. In a systemic model of murine acute myeloid leukemia (AML), tumor progression resulted in increased regulatory T cells (Treg) and elevation of program death-1 (PD-1) expression on CD8(+) cytotoxic T cells (CTLs) at the tumor site. PD-1 knockout mice were more resistant to AML despite the presence of similar percentage of Tregs compared with wild type. In vitro, intact Treg suppression of CD8(+) T-cell responses was dependent on PD-1 expression by T cells and Tregs and PD-L1 expression by antigen-presenting cells. In vivo, the function of adoptively transferred AML-reactive CTLs was reduced by AML-associated Tregs. Anti-PD-L1 monoclonal antibody treatment increased the proliferation and function of CTLs at tumor sites, reduced AML tumor burden, and resulted in long-term survivors. Treg depletion followed by PD-1/PD-L1 blockade showed superior efficacy for eradication of established AML. These data demonstrated that interaction between PD-1 and PD-L1 can facilitate Treg-induced suppression of T-effector cells and dampen the antitumor immune response. PD-1/PD-L1 blockade coupled with Treg depletion represents an important new approach that can be readily translated into the clinic to improve the therapeutic efficacy of adoptive AML-reactive CTLs in advanced AML disease. %B Blood %V 116 %P 2484-93 %8 2010 Oct 7 %G eng %N 14 %1 http://www.ncbi.nlm.nih.gov/pubmed/20570856?dopt=Abstract %R 10.1182/blood-2010-03-275446