Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer.
Small cell lung cancer (SCLC) is characteristically not associated with tumour-infiltrating lymphocytes. Since SCLC has been reported to show marked reduction of class I HLA, the reduced expression has been considered a means of escaping anti-cancer immunity. However, HLA-DR expressed in cancer cells is now known to contribute to anti-cancer immunity. To clarify the difference in HLA-DR expression between SCLC and non-small cell lung cancer (NSCLC), and the mechanism, the expression and the cis- and trans-acting factors involved were investigated. HLA-DR was not immunohistochemically detected in any SCLC and could not be induced by interferon gamma (IFN-gamma) in any SCLC cell line, whereas HLA-DR was expressed to varying degrees and was easily induced in NSCLC. SCLC cell lines lacked class II transactivator (CIITA) even after IFN-gamma induction, whereas NSCLC cell lines expressed CIITA. The other class II HLA-specific transcription factors were expressed and genomic DNA of HLA-DR, including the promoter, was conserved well both in SCLC and in NSCLC cell lines. CIITA transfection improved the expression of HLA-DR in SCLC. In conclusion, the lack of CIITA results in severe deficiency of HLA-DR expression in SCLC. Since CIITA has also been reported to induce class I HLA, CIITA transfection might make it possible to establish effective anti-cancer immunotherapy against SCLC through the up-regulation of class I and class II HLA.
Yazawa
T
T
Department of Pathology, Kensei General Hospital, Ibaraki, Japan.
Kamma
H
H
Fujiwara
M
M
Matsui
M
M
Horiguchi
H
H
Satoh
H
H
Fujimoto
M
M
Yokoyama
K
K
Ogata
T
T
D015152:Blotting, Northern; D015139:Blotting, Southern; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D006684:HLA-DR Antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D007371:Interferon-gamma