Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Oncotarget. 2010 Sep;1(5):329-38.

CD277 is a negative co-stimulatory molecule universally expressed by ovarian cancer microenvironmental cells.

Author information

  • 1Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.

Abstract

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 antigenpresenting 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.

KEYWORDS:

Tumor microenvironment; butyrophilin; dendritic cell; immune evasion; immunotherapy; tumor immunology

PMID:
21113407
[PubMed - indexed for MEDLINE]
PMCID:
PMC2992324
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Impact Journals, LLC Icon for PubMed Central
    Loading ...
    Write to the Help Desk