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Establishment of 15 Cancer Cell Lines From Patients With Lung Cancer and the Potential Tools for Immunotherapy^*

^* From the Second Department of Surgery (Drs. Sugaya, Takenoyama, Osaki, Yasuda, Sugio, and Yasumoto), University of Occupational and Environmental Health; and Department of Chest Surgery (Dr. Nagashima), Kitakyushu Municipal Medical Center, Kitakyushu, Japan.

Correspondence to: Masakazu Sugaya, MD, the Second Department of Surgery, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan; e-mail: sugaya{at}med.uoeh-u.ac.jp

Background: Since lung cancer is the major cause of death not only in Japan but in many other industrialized countries, the development of new therapeutic modalities is quite important. In patients with melanoma, immunotherapy with some tumor antigens has been shown to result in tumor regression. However, little is known about specific immune responses and tumor antigens in lung cancer, due to difficulty in establishing appropriate lung cancer cell lines. In order to resolve these difficulties, we tried to establish and characterize lung cancer cell lines as useful tools for the analysis of tumor-specific immune responses in patients with lung cancer.

Materials and methods: We tried to establish lung cancer cell lines from 549 patients with resectable lung cancer and from 21 patients with pleural and pericardial effusions or lymph node metastasis. We characterized the established cell lines after the induction of tumor-specific cytotoxic T lymphocytes (CTLs), and analyzed both the major histocompatibility complex (MHC) class I and class II molecules on their surfaces.

Results: We succeeded in establishing 15 lung cancer cell lines from 570 specimens (2.6%). The success rate of the establishment of lung cancer cell lines was significantly higher in patients at such advanced stages as MHC III and IV than in those at MHC stages I and II (p = 0.004). MHC class I molecules were expressed in 12 of 15 cell lines (80%), while MHC class II molecules were found in 3 of 15 cell lines (20%) on their cell surfaces by flow cytometry. A haplotype loss of MHC class I antigens was found in 6 of 15 cell lines (40%). Although CTLs were induced in only two of eight cell lines tried by stimulation with nontransduced autologous tumor cell lines, CTLs were successfully induced in all of eight cell lines tested by stimulation with CD80-transfected autologous tumor cells.

Conclusions: These results suggested that the tumor antigens recognized by CTLs could thus exist in the tumor cells derived from many lung cancer patients. It is, therefore, possible that antigen-specific immunotherapies may be potentially effective for patients with lung cancer by adoptive transfer of CTLs, as well as by vaccine therapy using tumor-specific antigens.

Key Words: cytotoxic T lymphocyte • lung cancer • major histocompatibility complex class I and class II • tumor cell line

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