Induced expression of B7-H4 on the surface of lung cancer cell by the tumor-associated macrophages: A potential mechanism of immune escape

B7-homolog 4 (B7-H4), a recently identified homolog of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H4 in lung cancer in vitro and in vivo. Although a lung cancer cell line constitutivel...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2012-04, Vol.317 (1), p.99-105
Main Authors: Chen, Cheng, Qu, Qiu-Xia, Shen, Yu, Mu, Chuan-Yong, Zhu, Yi-Bei, Zhang, Xue-Guang, Huang, Jian-An
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Antineoplastic Agents - pharmacology
B7-H4
blood proteins
Carcinoma, Lewis Lung - drug therapy
Carcinoma, Lewis Lung - genetics
Carcinoma, Lewis Lung - immunology
Carcinoma, Lewis Lung - pathology
Cell culture
Cell cycle
Cell Line, Tumor
coculture
Coculture Techniques
Culture Media, Conditioned - metabolism
Cytotoxicity, Immunologic
Female
Flow cytometry
gene expression
Hematology, Oncology and Palliative Medicine
Immune system
Interferon-gamma - metabolism
Interleukin-10 - metabolism
Lung cancer
lung neoplasms
Lymphocytes
Lymphocytes, Tumor-Infiltrating - drug effects
Lymphocytes, Tumor-Infiltrating - immunology
macrophages
Macrophages - drug effects
Macrophages - immunology
Mice
Mice, Inbred C57BL
Ovarian cancer
Polymerase chain reaction
RNA, Messenger - metabolism
T-lymphocytes
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
Tumor Escape - drug effects
Tumor Necrosis Factor-alpha - metabolism
Tumor-associated macrophages
Tumors
Up-Regulation
V-Set Domain-Containing T-Cell Activation Inhibitor 1 - antagonists & inhibitors
V-Set Domain-Containing T-Cell Activation Inhibitor 1 - genetics
V-Set Domain-Containing T-Cell Activation Inhibitor 1 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:B7-homolog 4 (B7-H4), a recently identified homolog of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H4 in lung cancer in vitro and in vivo. Although a lung cancer cell line constitutively expressed B7-H4 mRNA and protein in plasma, primary tumor cell isolated from the transplanted lung carcinoma model expressed B7-H4 on the surface. Interestingly, in transplanted lung carcinoma model, the expression of membrane-bound B7-H4 in tumor cells was increased as prolonging of tumor transformation. Exposure to tumor-associated macrophages strongly induced membrane-bound B7-H4 expression on the lung cancer cell line. To elucidate the functional significance of lung cancer-related B7-H4 expression, we performed co-culture experiments of lung cancer cell with allo-reactive T cells. Lung cancer-related B7-H4 was identified as a strong inhibitor of T-cell effect. Furthermore, B7-H4 mAb had an ability to inhibit tumor growth in vivo. B7-H4 expression may thus significantly influence the outcome of T-cell tumor cell interactions and TAM induced membrane-bound B7-H4 on the lung cancer cell represents a novel mechanism by which lung cancer cells evade immune recognition and destruction.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.11.017