Successful induction of tumor-specific cytotoxic T lymphocytes from patients with non-small cell lung cancer using CD80-transfected autologous tumor cells.
Cytotoxic T lymphocytes (CTL) against human lung cancer cells are difficult to induce by a conventional method using tumor cell stimulation probably due to an insufficiency of tumor antigens (TA) or costimulatory molecules such as CD80. We, therefore, investigated the potential of CD80-transfected tumor cells as stimulators of the in vitro induction of autologous tumor-specific CTL from regional lymph node lymphocytes in patients with lung cancer. Five non-small cell lung cancer cell lines (two adenocarcinomas, 1 squamous cell carcinoma, 1 large cell carcinoma and 1 adenosquamous cell carcinoma) were established from surgical specimens and were successfully transduced with a plasmid constructed with expression vector pBj and human CD80 cDNA, using a lipofection method. CD80-transfected tumor cells (CD80-AT) significantly augmented the proliferation of autologous lymphocytes from all cases as compared with non-transfected tumor cells (AT). AT-stimulated lymphocytes from 4 out of 5 cases did not show any cytotoxicity against AT; however, lymphocytes stimulated with CD80-AT exhibited substantial cytotoxicity against parental AT in all 5 cases tested. AT-stimulated lymphocytes derived from only one out of 5 cases showed major histocompatibility complex (MHC)-class I-restricted cytokine production in response to AT, while the MHC-class I-restricted responses were found in CD80-AT-stimulated lymphocytes from 4 out of 5 cases. These results indicate that CD80 on tumor cells could be a beneficial costimulatory molecule to elicit CTL against lung cancer, and also show that TA recognized by CTL was frequently expressed on lung cancer cells.
Department of Surgery II, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan. m-take@med.uoeh-u.ac.jp
M
M
Takenoyama
I
I
Yoshino
R
R
Eifuku
T
T
So
S
S
Imahayashi
M
M
Sugaya
M
M
Yasuda
M
M
Inoue
Y
Y
Ichiyoshi
T
T
Osaki
A
A
Nagashima
K
K
Nomoto
K
K
Yasumoto
D000230:Adenocarcinoma / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D018196:Carcinoma, Adenosquamous / Q000276:immunology; D018287:Carcinoma, Large Cell / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D011994:Recombinant Proteins