Identification of ribosomal protein L19 as a novel tumor antigen recognized by autologous cytotoxic T lymphocytes in lung adenocarcinoma.
The purpose of the present study was to identify a novel tumor-specific antigen capable of inducing a specific cellular immune response in lung cancer patients. The co-culture of regional lymph node lymphocytes and the CD80-transfected autologous lung adenocarcinoma cell line H1224L resulted in a successful induction of bulk cytotoxic T lymphocytes (CTL). CTL clone L7/8 was established by the limiting dilution method from these bulk CTLs and lysed H1224L but not autologous Epstein-Barr virus-transformed B cells or K562. The CTL clone also recognized allogeneic lung cancer cell lines in an HLA-A*31012-restricted manner. Using the CTL clone, an antigen-coding gene was identified using the cDNA expression cloning technique, which encodes ribosomal protein L19 (RPL19). Finally, a 9 mer antigenic peptide was identified by means of construction of mini-genes. RPL19 was overexpressed in the lung cancer tissue from patient H1224. All of the normal tissues examined expressed lower levels of RPL19 mRNA than that of the lung cancer tissue. RPL19 was also found to be overexpressed in 12 of 30 (40%) non-small-cell lung cancer tissues by immunohistochemical staining. The expression level of RPL19 in tumor cell lines correlated positively with the production of interferon (IFN)-gammaby CTL clone L7/8 in response to such cell lines. In addition, the suppression of RPL19 expression by transfection with small interfering RNA resulted in the suppression of cyclinD1, D3 synthesis, and the growth inhibition of lung cancer cell lines overexpressing RPL19. Therefore, this growth suppression could be ascribed to the inhibition of the cell cycle. These results may indicate that RPL19 is a novel overexpressed antigen which may therefore be a useful candidate as a target for specific immunotherapy.
Kuroda
Koji
K
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Takenoyama
Mitsuhiro
M
Baba
Tetsuro
T
Shigematsu
Yoshiki
Y
Shiota
Hironobu
H
Ichiki
Yoshinobu
Y
Yasuda
Manabu
M
Uramoto
Hidetaka
H
Hanagiri
Takeshi
T
Yasumoto
Kosei
K
D000230:Adenocarcinoma / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D012269:Ribosomal Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C069527:HLA-A31 antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C489092:RPL19 protein, human; D012269:Ribosomal Proteins