期刊
ONCOTARGET
卷 1, 期 5, 页码 329-338出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.165
关键词
Tumor microenvironment; tumor immunology; dendritic cell; immune evasion; butyrophilin; immunotherapy
资金
- Liz-Tilberis Award
- NCI [RO1CA124515, RO1CA124515-S, R21CA132026]
- John H. Copenhaver, Jr. and William H. Thomas, M. D. Fellowship
- Ruth L. Kirschstein National Research Service Award [F31CA134188]
- NCRR [P20RR018787]
CD277, a member of the butyrophilin subfamily 3 (BTN3), shares significant sequence similarities and predicted common structural features with inhibitory B7-H4 and other members of the B7 superfamily. Here we report that CD277 is consistently expressed in stromal, as well as tumor cells in the microenvironment of human advanced ovarian carcinoma specimens, both of primary and metastatic origin. MHC-II+ myeloid antigen-presenting leukocytes (dendritic cells and macrophages) express significantly higher levels of surface CD277, compared to other tumor-infiltrating leukocyte subsets, and this expression is significantly up-regulated by multiple common tumor microenvironmental signals, including VEGF and CCL3. Most importantly, engagement of CD277 on the surface of TCR-stimulated T cells inhibits their otherwise robust expansion and production of Th1 cytokines by preventing the up-regulation of cFLIP. Our results point to a role for CD277 up-regulated by microenvironmental signals in the acquisition of a regulatory phenotype by tumor-associated myeloid cells. Consequently, CD277, and likely other butyrophilins and butyrophilin-like molecules, emerge as regular players in the orchestration of immunosuppressive networks in ovarian cancer, and therefore new targets for interventions to overcome immune evasion and boost anti-tumor immunity in cancer patients.
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