B7-H3 and B7-H4 expression in non-small-cell lung cancer.
Inhibitory regulatory functions of B7-H3 and B7-H4 regarding T-cell activation have been reported recently. Little is known about the significance of human B7-H3 and B7-H4 expression in non-small-cell lung cancer (NSCLC), and we conducted the present study to address this issue in cell lines and tumor tissue from 70 patients. B7-H3 is over-expressed by all six NSCLC cell lines on both mRNA and protein level. B7-H4 is only transcripted by one cell line in which an alternatively spliced form was discovered. In tumor tissues, expression of B7-H3 and B7-H4 was found both on the cell membrane and in the cytoplasm. Thirty-seven percent of the specimens expressed B7-H3 and 43% B7-H4. The number of T infiltrating lymphoid cells (TILs) in the tumor tissues that expressed B7-H3 or B7-H4 was much lower than those who did not. There was a significant positive relation between the expression of B7-H3 and B7-H4, and high B7-H3 or B7-H4 expression was significantly more common in cases with lymph node metastasis. These observations suggest the contribution of B7-H3 and B7-H4 to immune dysfunction and tumor progression in NSCLC patients. B7-H3 and B7-H4 may be an important target for diagnosis and/or therapy of NSCLC.
Sun
Yuping
Y
Immunological Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm S-17176, Sweden.
Wang
Yunshan
Y
Zhao
Jianqiang
J
Gu
Ming
M
Giscombe
Ricardo
R
Lefvert
Ann Kari
AK
Wang
Xiongbiao
X
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D017493:Leukocyte Common Antigens