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Haplotype loss of HLA class I antigen as an escape mechanism from immune attack in lung cancer.

Abstract
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.
AuthorsTetsuya So, Mitsuhiro Takenoyama, Makiko Mizukami, Yoshinobu Ichiki, Masakazu Sugaya, Takeshi Hanagiri, Kenji Sugio, Kosei Yasumoto
JournalCancer research (Cancer Res) Vol. 65 Issue 13 Pg. 5945-52 (Jul 1 2005) ISSN: 0008-5472 [Print] United States
PMID15994973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Cycle Proteins
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-B Antigens
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • SUGT1 protein, human
Topics
  • Amino Acid Sequence
  • Carcinoma, Large Cell (genetics, immunology, pathology)
  • Cell Cycle Proteins (immunology)
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 6 (genetics)
  • Epitopes, T-Lymphocyte (immunology)
  • HLA-A Antigens (genetics, immunology)
  • HLA-B Antigens (genetics, immunology)
  • Haplotypes
  • Humans
  • Loss of Heterozygosity
  • Lung Neoplasms (genetics, immunology, pathology)
  • Peptide Fragments (immunology)
  • Receptors, Antigen, T-Cell (immunology)
  • T-Lymphocytes, Cytotoxic (cytology, immunology)
  • Transfection

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