Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology, human leukocyte antigen class I loss and interleukin-10 production.
Immune evasion in lung cancer results from both structural and functional alterations of human leukocyte antigen (HLA) class I molecules and the local release of immunosuppressive cytokines. Recent data suggest that HLA-G, a nonclassical class Ib molecule, is involved in immune evasion by tumor cells. We sought to determine whether HLA-G could contribute to immunescape in lung cancer. All of 19 tumor specimens examined demonstrated detectable membrane-bound (HLA-G1), as well as soluble (HLA-G5) isoform transcription. Nine of 34 (26%) tumors were positive by immunohistochemistry using monoclonal antibody (mAb) 4H84, recognizing all denatured HLA-G isoforms, of which six were positive using mAb 16G1, recognizing soluble HLA-G. HLA-G immunoreactivity correlated with high-grade histology, with HLA-G being preferentially expressed on large-cell carcinomas. In these patients, loss of classical HLA class I molecules was observed to associate with HLA-G protein up-regulation. Moreover, we found interleukin-10 expressed in 15 of 34 (44%) tumors, and in most of the HLA-G-positive cases (7 of 9), suggesting up-modulation of HLA-G by interleukin-10. It is conceivable that HLA-G expression in lung cancer might be one of the ways how the tumor down-regulates host immune response, in addition to interleukin-10 production and HLA class I loss.
Urosevic
M
M
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Kurrer
M O
MO
Kamarashev
J
J
Mueller
B
B
Weder
W
W
Burg
G
G
Stahel
R A
RA
Dummer
R
R
Trojan
A
A
D000368:Aged; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D012333:RNA, Messenger; D016753:Interleukin-10