High frequency of allele-specific down-regulation of HLA class I expression in lung cancer cell lines.
Loss or down-regulation of HLA expression has been demonstrated in various types of solid tumors and is considered to be one of the mechanisms of tumor immunoescape. The effectiveness of immunotherapy using tumor-specific antigens (TSA) largely depends on the expression of the appropriate HLA class I alleles on the tumor cells. We analyzed the allele-specific HLA class I surface expression of six lung cancer cell lines using a broad panel of allele-specific monoclonal antibodies, as well as the effect of IFN-gamma on HLA expression. Flow cytometric analysis displayed a wide range, from minimal to a high degree of expression of monomorphic HLA class I among the studied cell lines. Allele-specific loss or down-regulation of HLA also was observed in 5 out of 6 cell lines. Our results suggest that lung cancer patients considered for specific immunotherapy should be examined with respect to the expression of specific HLA class I allele binding the TSA.
Department of Respiratory Medicine, National Sanyo Hospital, Respiratory Disease Center, Ube 755-0241, Japan.
Akio
A
Hiraki
Nobuharu
N
Fujii
Tomoyuki
T
Murakami
Katsuyuki
K
Kiura
Keisuke
K
Aoe
Hiromichi
H
Yamane
Kozo
K
Masuda
Tadashi
T
Maeda
Kazuro
K
Sugi
Zbigniew
Z
Darzynkiewicz
Mitsune
M
Tanimoto
Mine
M
Harada
D000483:Alleles; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I