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.
Takenoyama
M
M
Department of Surgery II, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan. m-take@med.uoeh-u.ac.jp
Yoshino
I
I
Eifuku
R
R
So
T
T
Imahayashi
S
S
Sugaya
M
M
Yasuda
M
M
Inoue
M
M
Ichiyoshi
Y
Y
Osaki
T
T
Nagashima
A
A
Nomoto
K
K
Yasumoto
K
K
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