Autologous tumor-specific cytotoxic T lymphocytes in a patient with lung adenocarcinoma: implications of the shared antigens expressed in HLA-A24 lung cancer cells.
Human lung adenocarcinoma-specific cytotoxic T lymphocytes (CTL) were generated by multiple stimulations with autologous tumor cells (named A110L) from regional lymph node lymphocytes and tumor-infiltrating lymphocytes expanded by solid-phase anti-CD3 monoclonal antibody (mAb) and recombinant interleukin-2. The CTL lysed A110L but failed to kill either autologous B lymphocytes immortalized by the Epstein-Barr virus or K562. The killing activity of the CTL against autologous A110L was inhibited by anti-MHC class I mAb (W6/32), but not by anti-MHC class II mAb. The CTL produced interferon-gamma and GM-CSF in response to A110L and the production was completely blocked by the addition of anti-MHC class I mAb. The HLA type of the CTL was HLA-A2/A24, B52/B54, Cw1/-. Allele-specific deletion of HLA-A2 molecules was observed in A110L by staining with anti-HLA-A2 mAb. A partial blocking effect on the cytokine production from the CTL was also obtained with anti-CD8, and anti-HLA-A24 mAbs, but not with anti-MHC class II, anti-CD4 and anti-HLA-A2 mAbs. To analyze further the mechanism of antigen recognition by the CTL, the cross reactivity of the CTL against several HLA-A locus-matched (HLA-A24+) and mismatched allogeneic tumor cells (HLA-A24-) was investigated. The A110L-specific CTL showed a weak but significant cytotoxicity against some HLA-A24 positive lung cancer cell lines, such as Sq-1 (HLA-A11/A24, squamous cell carcinoma) and PC-9 (HLA-A2/A24, adenocarcinoma), but failed to kill HLA-A locus-mismatched allogeneic tumors. This cross reactivity of the CTL against Sq-1 and PC-9 was blocked by anti-MHC class I mAb. These results thus demonstrate that shared common tumor antigens might exist among lung cancer cells in the context of HLA-A24.
Takenoyama
M
M
Department of Surgery II, University of Occupational and Environmental Health, Kitakyushu.
Yoshino
I
I
Fujie
H
H
Hanagiri
T
T
Yoshimatsu
T
T
Imabayashi
S
S
Eifuku
R
R
Nomoto
K
K
Yasumoto
K
K
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D019138:Antibodies, Blocking / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D015234:HLA-A Antigens; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor