Abstract
We analyzed the phenotype and cytotoxic ability of pleural exudative lymphocytes (PLEL) which were obtained from 18 advanced lung cancer patients. Freshly isolated PLEL were mainly CD4(+) T cells and had weak natural killer, autologous tumor killing and lymphokine‐activated killer activities. After cultivation of PLEL with interleukin‐2, cytotoxicity of PLEL against autologous tumor cells was increased at 2 weeks, but it was remarkably reduced at 4 weeks. When PLEL were stimulated by mitomycin C‐treated autologous tumor cells during culture, autologous tumor killing activity of PLEL was significantly enhanced even after 4 weeks of cultivation. Cold target inhibition analysis and binding inhibition assays using monoclonal antibodies indicated that autologous tumor stimulation could induce major histocompatibility complex class I restricted cytotoxic T lymphocytes specific for autologous tumor cells in some cases.
Keywords: Lung cancer, Pleural exudative lymphocytes, Cytotoxic T lymphocytes, Autologous tumor stimulation
Full Text
The Full Text of this article is available as a PDF (938.7 KB).
References
- 1.Shimogawara, I., Imamura, M., Yamanaka, N., Ishii, Y. and Kikuchi, K.Identification of lymphocyte subpopulations in human breast cancer tissues and its significance: an immunoperoxidase study with antihuman T‐ and B‐cell sera. Cancer, 49, 1456–1464 (1982). [DOI] [PubMed] [Google Scholar]
- 2.Hiratsuka, H., Imamura, M., Ishii, Y. and Kikuchi, K.Immunohistologic detection of lymphocyte subpopulations infiltrating in human oral cancer with special reference to its clinical significance. Am. J. Clin. Pathol., 81, 464–472 (1984). [DOI] [PubMed] [Google Scholar]
- 3.Ibayashi, Y., Uede, T., Uede, T. and Kikuchi, K.Functional analysis of mononuclear cells infiltrating into tumors: differential cytotoxicity of mononuclear cells from tumors of immune and non‐immune rats. J. Immunol., 134, 648–653 (1985). [PubMed] [Google Scholar]
- 4.Uede, T., Kohda, H., Ibayashi, Y., Osawa, H., Diamanstein, T. and Kikuchi, K.Functional analysis of mononuclear cells infiltrating into tumors: II. Differential ability of mononuclear cells obtained from various tissues to produce helper factors that are involved in the generation of cytotoxic cells. J. Immunol., 135, 3243–3259 (1985). [PubMed] [Google Scholar]
- 5.Murakami, T., Uede, T., Shijubo, N., Torimoto, Y., Ide, T., Sugimura, K., Azuma, I., Takai, Y. and Kikuchi, K.Functional analysis of mononuclear cells infiltrating into tumors: IV. Purification and functional characterization of cytotoxic cell generating factor. J. Immunol., 141, 4235–4242 (1988). [PubMed] [Google Scholar]
- 6.Shijubo, N., Uede, T. and Kikuchi, K.Functional analysis of mononuclear cells infiltrating into tumors: V. A soluble factors involved in the regulation of cytotoxic/suppressor T cell infiltration into tumors. J. Immunol., 142, 2961–2967 (1989). [PubMed] [Google Scholar]
- 7.Rosenberg, S. A., Lotze, M. T., Muul, L. M., Chang, A. E., Avis, F. P., Leitman, S., Linehan, W. M., Robertson, C. N., Lee, R. E., Rubin, J. T., Seipp, C. A., Simpson, C. G. and White, D. E.A progress report on the treatment of 157 patients with advanced cancer using lymphokine‐activated killer cells and interleukin 2 alone. N. Eng. J. Med., 316, 889–897 (1987). [DOI] [PubMed] [Google Scholar]
- 8.Rabinowich, H., Cohen, R., Bruderman, I., Steiner, Z. and Klajman, A.Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human cells by cultured infiltrating lymphocytes. Cancer Res., 47, 173–177 (1987). [PubMed] [Google Scholar]
- 9.Blanchard, D. K., Kavanagh, J. J., Joseph, G., Sinkovics, J. G., Cavanagh, D., Hewitt, S. M. and Djeu, J. Y.Infiltration of interleukin‐2‐inducible killer cells in ascitic and pleural effusions of advanced cancer patients. Cancer Res., 48, 6321–6327 (1988). [PubMed] [Google Scholar]
- 10.Sato, T., Sato, N., Takahashi, S., Koshiba, H. and Kikuchi, K.Specific cytotoxicity of a long‐term cultured T‐cell clone on human autologous mammary cancer cells. Cancer Res., 46, 4384–4389 (1986). [PubMed] [Google Scholar]
- 11.Inoue, Y., Shijubo, N., Suzuki, A., Uede, T. and Kikuchi, K.Functional analysis of pleural exudative lymphocytes obtained from advanced lung cancer patients. Proc. Jpn. Cancer Assoc., 48th Annu. Meet, 268 (1989).
- 12.Kon, S., Takami, T., Ishii, Y. and Kikuchi, K.Differential effect of interferon on expression of HLA and human TL‐like (HTL) antigens on human lymphoid cells. Proc. Jpn. Soc. Immunol., 12, 36 (1982). [Google Scholar]
- 13.O'Connell, J. P., Kris, M. G., Gralla, R. J., Groshen, S., Trust, A., Fiare, J. J., Kelsen, D. P., Heelan, R. T. and Golbey, R. B.Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non‐small‐cell‐lung cancer treated with combination chemotherapy. J. Clin. Oncol., 4, 1604–1614 (1986). [DOI] [PubMed] [Google Scholar]
- 14.Sorensen, J. B.Prognostic factors in adenocarcinoma of the lung In“Basic and Clinical Concepts of Lung Cancer,” ed. Hansen H. H., pp. 215–243 (1989). Kluwer Academic Publishers, Boston, Mass. [Google Scholar]
- 15.Takita, H.Immunotherapy of lung cancer: a review. Int. Adv. Surg. Oncol., 6, 229–256 (1983). [PubMed] [Google Scholar]
- 16.Twentyman, P. R., Workman, P., Wright, K. and Bleenhen, N. M.The effects of alpha and gamma interferons on human lung cancer cells grown in vitro or as xenografts in nude mice. Br. J. Cancer, 52, 21–29 (1985). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Hollinshead, A., Stewart, T. H. M., Takita, H., Dalbow, M. and Concannon, J.Adjuvant specific active lung immunotherapy trials tumor asscociated antigens. Cancer, 60, 1249–1262 (1987). [DOI] [PubMed] [Google Scholar]
- 18.Rosenberg, S. A., Spiess, P. J. and Lafreiere, R.A new approach to the adoptive immunotherapy of cancer with tumor infiltrating lymphocytes. Science, 233, 1318–1321 (1986). [DOI] [PubMed] [Google Scholar]
- 19.Topalian, S. L., Solomon, D., Avis, F. P., Chang, A. E., Freerksen, D. L., Linehan, W. M., Lotze, M. T., Robertson, C. N., Seipp, C. N., Simon, P., Simpson, C. G. and Rosenberg, S. A.Immunotherapy of patients with advanced cancer using tumor infiltrating lymphocytes and recombinant interleukin‐2: a pilot study. J. Clin. Oncol., 6, 839–853 (1988). [DOI] [PubMed] [Google Scholar]
- 20.Shijubo, N., Uede, T., Nomura, N. and Kikuchi, K.Functional analysis of mononuclear cells infiltrating into tumors: establishment of a new system to obtain functionally active tumor‐infiltrating cells. Jpn. J. Cancer Res., 81, 28–34 (1990). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Itoh, K., Tilden, A. B. and Balch, C. M.Interleukin 2 activation of cytotoxic T lymphocytes infiltrating into human metastatic melanomas. Cancer Res., 46, 3011–3017 (1986). [PubMed] [Google Scholar]
- 22.Belldegrun, A., Kasid, A., Uppenkamp, M., Topalian, S. L. and Rosenberg, S. A.Human tumor infiltrating lymphocytes: analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. J. Immunol., 142, 4520–4526 (1989). [PubMed] [Google Scholar]
- 23.Kikuchi, Y., Kato, R., Sano, Y., Takahashi, H., Kanatani, T. and Takatsu, K.Generation of cytotoxic T lymphocytes from thymocyte precursors to trinitrophenyl‐modified self antigens: II. Establishment of a T cell hybrid clone constitutively producing killer‐helper factor(s) (KHF) and functional analysis of released KHF. J. Immunol., 136, 3553–3560 (1986). [PubMed] [Google Scholar]