Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer.
One of tumor escape mechanisms from the host's immunosurveillance system (i.e., a haplotype loss of HLA class I antigens) has been detected in various tumor cells. We hypothesize that the majority of tumor cells with normal HLA class I expression were attacked and eradicated by CTLs, and only a minority with an abnormal expression of HLA class I antigens could escape the host's immunosurveillance system. Using HLA class I-transfected tumor variants as stimulators in A904L lung cancer cell line, which has a haplotype loss of HLA class I antigens, both the transfected HLA-A26 and HLA-B39-restricted CTL lines were induced from autologous lymphocytes. However, only one HLA-B39-restricted CTL clone (CTL G3b) was established, and it was then used to identify the antigen. SGT1B [suppressor of G2 allele of SKP1 (SGT1), suppressor of kinetochore protein (SKP1)] was identified as the antigen recognized by CTL G3b. Further experiments using 13 subclones from a primary culture of A904L were found to confirm our above-mentioned hypothesis. Tumor cells with a normal HLA class I expression may thus be killed by CTL at an early stage of carcinogenesis, and only tumor cells with a haplotype loss of HLA class I antigens can escape an immune attack and develop into clinical cancer.
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Kitakyushu, Japan. tetsuya@med.uoeh-u.ac.jp
Tetsuya
T
So
Mitsuhiro
M
Takenoyama
Makiko
M
Mizukami
Yoshinobu
Y
Ichiki
Masakazu
M
Sugaya
Takeshi
T
Hanagiri
Kenji
K
Sugio
Kosei
K
Yasumoto
D000595:Amino Acid Sequence; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000276:immunology; D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D014162:Transfection
D018797:Cell Cycle Proteins; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C490164:SUGT1 protein, human