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

Autor: Yolanda Nesbeth, Jose R. Conejo-Garcia, Diana Martinez, Uciane K. Scarlett, Juan R. Cubillos-Ruiz, Melanie R. Rutkowski, Ana L. Camposeco-Jacobs
Rok vydání: 2010
Předmět:
Models
Molecular
Myeloid
Protein Conformation
medicine.medical_treatment
T-Lymphocytes
CASP8 and FADD-Like Apoptosis Regulating Protein
Lymphocyte Activation
0302 clinical medicine
Tumor Microenvironment
tumor immunology
Ovarian Neoplasms
0303 health sciences
Membrane Glycoproteins
Research Papers
Cell Hypoxia
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cytokines
Female
immunotherapy
Inflammation Mediators
Stromal cell
butyrophilin
dendritic cell
Molecular Sequence Data
Antigen-Presenting Cells
Biology
Transfection
03 medical and health sciences
Structure-Activity Relationship
Immune system
Antigens
CD
medicine
Humans
Amino Acid Sequence
Antigen-presenting cell
030304 developmental biology
Cell Proliferation
immune evasion
Tumor microenvironment
Butyrophilins
Macrophages
Dendritic cell
Immunotherapy
Dendritic Cells
medicine.disease
Coculture Techniques
Immunology
Stromal Cells
Ovarian cancer
K562 Cells
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: Received: August 7, 2010 , Accepted: August 25, 2010 , Published: September 11, 2010 // 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.
Databáze: OpenAIRE
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