期刊
JOURNAL FOR IMMUNOTHERAPY OF CANCER
卷 2, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/2051-1426-2-8
关键词
T cells; Tumor immunity; Dendritic cells; Inflammation
资金
- NIH/NCI [K01-CA111402, RO1-CA123396, R01 CA 112358]
- Eli & Edyth Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
- STOP Cancer Foundation
- Ben & Catherine Ivy Foundation
- NIH (National Institutes of Health) [CA16042, CA-16042, AI-28697]
- UCLA AIDS
- NATIONAL CANCER INSTITUTE [P30CA016042] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R25NS079198] Funding Source: NIH RePORTER
Background: Histone deacetylase (HDAC) inhibitors are a class of agents that have potent antitumor activity with a reported ability to upregulate MHC and costimulatory molecule expression. We hypothesized that epigenetic pharmacological immunomodulation could sensitize tumors to immune mediated cell death with an adoptive T cell therapy. Methods: The pan-HDAC inhibitor, LBH589, was combined with gp100 specific T cell immunotherapy in an in vivo B16 melanoma model and in an in vivo non-tumor bearing model. Tumor regression, tumor specific T cell function and phenotype, and serum cytokine levels were evaluated. Results: Addition of LBH589 to an adoptive cell transfer therapy significantly decreased tumor burden while sustaining systemic pro-inflammatory levels. Furthermore, LBH589 was able to enhance gp100 specific T cell survival and significantly decrease T regulatory cell populations systemically and intratumorally. Even in the absence of tumor, LBH589 was able to enhance the proliferation, retention, and polyfunctional status of tumor specific T cells, suggesting its effects were T cell specific. In addition, LBH589 induced significantly higher levels of the IL-2 receptor (CD25) and the co-stimulatory molecule OX-40 in T cells. Conclusion: These results demonstrate that immunomodulation of adoptively transferred T cells by LBH589 provides a novel mechanism to increase in vivo antitumor efficacy of effector CD8 T cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据