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.

• Authors: Tetsuya So, Mitsuhiro Takenoyama, Makiko Mizukami, Yoshinobu Ichiki, Masakazu Sugaya, Takeshi Hanagiri, Kenji Sugio, Kosei Yasumoto
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 13 Pg. 5945-52 (Jul 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 15994973 (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