Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Sep;86(9):861–866. doi: 10.1111/j.1349-7006.1995.tb03097.x

Granulocyte‐Macrophage Colony‐stimulating Factor Augments Lymphokine‐activated Killer Activity from Pleural Cavity Mononuclear Cells of Lung Cancer Patients without Malignant Effusion

Keiji Takahashi 1,, Saburo Sone 2, Seiya Saito 1, Yoshitaka Kamamura 1, Tadashi Uyama 1, Takeshi Ogura 2, Yasumasa Monden 1
PMCID: PMC5920930  PMID: 7591964

Abstract

The role of recombinant granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in augmentation of lymphokine‐activated killer (LAK) cell induction by interleukin‐2 (IL‐2) from pleural cavity mononuclear cells (PCMNCs) was examined in sixteen patients with resectable primary lung cancer not associated with malignant effusion. None of the patients had received any anticancer therapy prior to this study. Incubation of PCMNCs of patients without malignant effusion with GM‐CSF for 4 days in the presence of IL‐2 resulted in a significant increase in LAK activity against natural killer‐resistant Daudi cells. This result was obtained by using the 4 h 51Cr‐release assay. PCMNCs and blood mononuclear cells (BMNCs) were harvested simultaneously from pleural cavity lavage fluid and peripheral blood in lung cancer patients. The LAK activity developed from PCMNCs and BMNCs following incubation with IL‐2 for 4 days, but the LAK activity from PCMNCs was significantly lower than that from BMNCs (P < 0.05). Incubation of PCMNCs with GM‐CSF augmented the LAK activity from PCMNCs to a level as high as that from BMNCs. These results suggest that the combined use of GM‐CSF with IL‐2 may result in augmentation of LAK activity developed from PCMNCs of lung cancer patients without malignant effusion.

Keywords: GM‐CSF, LAK, IL‐2, Mononuclear cell, Lung cancer

Full Text

The Full Text of this article is available as a PDF (403.7 KB).

REFERENCES

  • 1. ) Grooman , J. E. , Molina , J.‐M. and Scadden , D. T.Hematopoietic growth factors . N. Engl. J. Med. , 321 , 1449 – 1459 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Sieffk , C. A.Hematopoietic growth factor . J. Clin. Invest. , 79 , 1549 – 1557 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) Chen , B. D. , Clark , C. R. and Chou , T.Granulocyte/macrophage colony‐stimulating factor stimulates monocytes and tissue macrophage proliferation and enhances their responsiveness to macrophage colony stimulating factor . J. Immunol. , 141 , 139 – 144 ( 1988. ). [PubMed] [Google Scholar]
  • 4. ) Falk , L. A. , Wahl , L. M. and Vogel , S. M.Analysis of Ia antigen expression in macrophages derived from bone marrow cells cultured with granulocyte‐macrophage colony stimulating factor . J. Immunol. , 140 , 2652 – 2660 ( 1988. ). [PubMed] [Google Scholar]
  • 5. ) Hancock , W. W. , Pleau , M. E. and Kobzik , L.Recombinant granulocyte‐macrophage colony‐stimulating factor down‐regulates expression of IL‐2 receptor on the human mononuclear phagocytes by induction of prostaglandin . J. Immunol. , 140 , 3021 – 3025 ( 1988. ). [PubMed] [Google Scholar]
  • 6. ) Hinuma , S. , Onda , H. , Naruo , K. , Ichimori , Y. , Koyama , M. and Tsukatomo , K.Translation of interleukin 2 mRNA from human peripheral blood leukocytes in Xenopus oocytes . Biochem. Biophys. Res. Commun. , 109 , 363 – 369 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Herrmann , F. and Schultz , E.Hematopoietic responses in patients with advanced malignancy treated with recombinant human‐granulocyte macrophage colony stimulating factor . J. Clin. Oncol. , 7 , 159 – 167 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Lozte , M. T. , Grimm , E. A. , Maunder , A. , Strausser , J. L. and Rosenberg , S. A.Lysis of fresh and cultured autologous tumor by human lymphocytes cultured with T‐cell growth factor . Cancer Res. , 41 , 4420 – 4425 ( 1981. ). [PubMed] [Google Scholar]
  • 9. ) Grimm , E. A. , Mazumder , A. , Zhang , H. Z. and Rosenberg , S. A.Lymphokine‐activated killer cell phenomenon: lysis of natural killer‐resistant fresh solid tumor cells by interleukin‐2 activated autologous human peripheral blood lymphocytes . J. Exp. Med. , 155 , 1823 – 1841 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. ) Weiss , G. R. , Margolin , K. A. , Aronson , F. R. , Sznol , M. , Atkins , M. B. , Ducher , J. P. , Gaynor , E. R. , Boldt , D. H. , Doroshow , J. H. , Bar , M. H. , Hawkins , M. J. , Demchak , P. A. , Gucalp , R. and Fisher , R.A randomized phase II trial of continuous infusion interleukin‐2 or bolus injection interleukin‐2 plus lymphokine‐activated killer cells for advanced renal cell carcinoma . J. Clin, Oncol. , 10 , 257 – 281 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Ikarashi , H. , Fujita , K. , Takakuwa , K. , Kodama , S. , Tokunaga , A. , Takahashi , T. and Tanaka , K.Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor‐infiltrating lymphocytes . Cancer Res. , 54 , 190 – 196 ( 1994. ). [PubMed] [Google Scholar]
  • 12. ) Takahashi , K. , Sone , S. , Kimura , S. , Ogura , S. and Monden , Y.Phenotypes and lymphokine activated killer activity of pleural cavity lymphocytes of lung cancer patients without malignant effusion . Chest , 103 , 1732 – 1738 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Yanagawa , H. , Sone , S. , Nii , A. , Fukuta , K. , Nakanishi , M. , Maeda , K. , Honda , M. and Ogura , T.Lymphokine‐activated killer induction and its regulation by macro‐phages in malignant pleural effusions . Jpn. J. Cancer Res. , 80 , 1220 – 1227 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Itoh , K. , Shiba , K. , Shimizu , Y. , Suzuki , R. and Kumagai , K.Generation of activated killer (AK) cells by recombinant interleukin‐2 (IL‐2) in collaboration with interferon‐γ (IFN‐γ) . J. Immunol. , 134 , 3124 – 3129 ( 1985. ). [PubMed] [Google Scholar]
  • 15. ) Brunda , M. , Tarnowsky , D. and Davatelis , V.Interaction of recombinant interferons with interleukin‐2: differential effects of natural killer cell activity and interleukin‐2‐activated killer cells . Int. J. Cancer , 37 , 787 – 793 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Ochoa , A. , Gromo , G. , Barbara , B. J. , Sondel , P. M. and Bach , F. H.Long term growth of lymphokine‐activated killer (LAK) cells: role of anti‐CD3, β‐IL‐1, interferon‐γ andβ . J. Immunol. , 138 , 2728 – 2733 ( 1987. ). [PubMed] [Google Scholar]
  • 17. ) Owen‐Schaub , L. B. , Gutterman , J. U. and Grimm , E. A.Synergy of tumor necrosis factor and interleukin 2 in the activation of human cytotoxic lymphocytes: effect of tumor necrosis factor a and interleukin 2 in the generation of human lymphokine‐activated killer cell cytotoxicity . Cancer Res. , 48 , 788 – 792 ( 1988. ). [PubMed] [Google Scholar]
  • 18. ) Sone , S. , Utsugi , T. , Nii , A. and Ogura , T.Differential effects of recombinant interferon α, β and γ on the induction of human lymphokine(IL‐2)‐activated killer activity . J. Natl. Cancer Inst. , 80 , 425 – 431 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Singh , S. M. , Sone , S. , Inamura , N. and Ogura , T.Upregulation by granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) of induction of lymphokine (IL‐2)‐activated killer (LAK) cells by human blood monocytes . Int. J. Cancer , 44 , 170 – 176 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Kato , K. , Yamada , T. , Kawahara , K. , Onda , H. , Asano , T. and Sagino , H.Purification and characterization recombinant human interleukin‐2 produced in Escherichia coli . Biophys. Res. , 31 , 692 – 699 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Vadhan‐Raj , S. , Broxmeyer , H. E. , Hittleman , W. N. , Papadopoulos , N. E. , Plager , C. , Salm , P. A. , Gutterman , J. U. and Benjamin , R. S.Abrogating chemotherapy (CT)‐induced myelosuppression by GM‐CSF: optimizing the schedule . Proc. Am. Soc. Clin. Oncol. , 10 , 349 ( 1991. ). [Google Scholar]
  • 22. ) Shaffer , D. W. , Smith , L. S. , Burris , H. A. , Clark , G. M. , Eckardt , J. R. , Field , S. M. , Weiss , G. R. , Rinaldi , D. A. , Bowen , K. J. , Kuhn , J. G. and von Hoff , D. D.A randomized phase I trial of chronic oral etoposide with or without granulocyte‐macrophage colony‐stimulating factor in patients with advanced malignancies . Cancer Res. , 53 , 5929 – 5933 ( 1993. ). [PubMed] [Google Scholar]
  • 23. ) Koyama , S. and Fukao , K.Phenotypic analysis of nylon‐wool‐adherent suppressor cells that inhibit the effector process of tumor cell lysis by lymphokine‐activated killer cells in patients with advanced gastric carcinoma . J. Cancer Res. Clin. Oncol. , 120 , 240 – 247 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Reynold , J. V. , Somes , S. S. and Gaillou , P. J.Inhibition of interleukin‐2 dependent immune responses by serum from patients with advanced gastrointestinal cancer . J. Surg. Oncol. , 2 , 227 – 234 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Lanier , L. L. , Benike , C. J. , Phillips , J. H. and Engleman , E. G.Recombinant interleukin 2 enhanced natural killer cell‐mediated cytotoxicity in human lymphocyte sub‐populations expressing the Leu 7 and Leu 11 antigens . J. Immunol. , 134 , 794 – 801 ( 1985. ). [PubMed] [Google Scholar]
  • 26. ) Itoh , K. , Tilden , A. B. , Kumagai , K. and Balch , C. M.Leu‐11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL‐2)‐induced activated killer (AK) cell . J. Immunol. , 134 , 802 – 807 ( 1985. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES