Skip to main content
NCBI home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1989 Aug;29(4):288–292. doi: 10.1007/BF00199217

Granulocyte-monocyte-colony-stimulating factor augments the cytotoxic capacity of lymphocytes and monocytes in antibody-dependent cellular cytotoxicity

G Masucci 1, P Wersäll 1, P Ragnhammar 1, H Mellstedt 1,✉
PMCID: PMC11038059  PMID: 2665935

Abstract

Human peripheral blood mononuclear cells (lymphocytes and monocytes) were preincubated for 0–24 h with human recombinant granulocyte-monocyte-colony-stimulating factor (GM-CSF) and used as effector cells in an 18 h antibody-dependent cellular cytotoxicity (ADCC) assay with SW948 (a human colorectal carcinoma cell line) as target cells and mAb 17-1A. A significant increase in the lytic capability was noted after 0.5–2 h of preactivation while longer preincubation times did not significantly increase the lytic potential. GM-CSF at 0.01 μg/ml induced the best tumor cell lysis while higher concentrations were inhibitory. GM-CSF pretreatment induced a statistically significant increase in the lytic capacity of both monocytes and lymphocytes in ADCC as well as in the spontaneous cytotoxicity.

Keywords: Target Cell, Peripheral Blood Mononuclear Cell, Colorectal Carcinoma, Effector Cell, Carcinoma Cell Line

References

  • 1.Adams D, Hall T, Steplewski Z, Koprowski H. Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis. Proc Natl Acad Sci USA. 1984;81:3506. doi: 10.1073/pnas.81.11.3506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Böyum A. A one stage procedure for isolation of granulocytes and lymphocytes from human blood. Scand J Clin Lab Invest. 1968;21:77. [PubMed] [Google Scholar]
  • 3.Böyum A. Isolation of human blood monocytes with Nycodenz, a new non-ionic iodinated gradient medium. Scand J Immunol. 1983;17:429. doi: 10.1111/j.1365-3083.1983.tb00809.x. [DOI] [PubMed] [Google Scholar]
  • 4.Donahue RE, Wang EA, Stone DK, Wong GG, Sehgal PK, Nathan DG, Clark SC. Stimulation of hematopoesis in primates by continuous infusion of recombinant human GM-CSF. Nature. 1986;321:872. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
  • 5.Fabian I, Baldwin GC, Golde DW. Biosynthetic granulocyte-macrophage colony-stimulating factor enhances neutrophil cytotoxicity toward human leukemia cells. Leukemia. 1987;8:613. [PubMed] [Google Scholar]
  • 6.Fleischmann J, Golde DW, Weisbart RH, Gasson JC. Granulocyte macrophage colony-stimulating factor enhancing phagocytosis of bacteria by human neutrophils. Blood. 1983;68:708. [PubMed] [Google Scholar]
  • 7.Frödin J-E, Pihlstedt P, Lefvert AK, Mellstedt H. Isolation and characterization of autologous blood mononuclear cells used for auto-infusion together with monoclonal anti-bodies in tumor treatment. Hybridoma. 1987;6:555. doi: 10.1089/hyb.1987.6.555. [DOI] [PubMed] [Google Scholar]
  • 8.Gasson JC, Weisbart RH, Kaufman SE, Clark SC, Hewick RM, Wong GG, Golde DW. Purified human granulocyte-macrophage colony-stimulating factor: direct action on neutrophils. Science. 1984;226:1339. doi: 10.1126/science.6390681. [DOI] [PubMed] [Google Scholar]
  • 9.Grabstein KH, Urdal DL, Tushinski RJ, Mochizuki DY, Price VJ, Cantrell MA, Gillis S, Conlon PJ. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony stimulating factor. Science. 1986;232:506. doi: 10.1126/science.3083507. [DOI] [PubMed] [Google Scholar]
  • 10.Groupman JE, Mitsuyasu RT, DeLeo MJ, Oette DH, Golde DW. Effect of recombinant human granulocyte macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987;317:593. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
  • 11.Hancock WW, Pleau ME, Kobzik L. Recombinant granulocyte-macrophage colony-stimulating factor downregulates expression of IL-2 receptor on human mononuclear phagocytes by modulation of prostaglandin. J Immunol. 1988;40:3021. [PubMed] [Google Scholar]
  • 12.Herlyn D, Herlyn M, Steplewski Z, Koprowski H. Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma. Eur J Immunol. 1979;9:657. doi: 10.1002/eji.1830090817. [DOI] [PubMed] [Google Scholar]
  • 13.Holm G, Perlmann P. Quantitative studies on phytohaemaglutinin-induced cytotoxicity by normal human lymphocytes against homologous cells in tissue culture. Immunology. 1967;12:525. [PMC free article] [PubMed] [Google Scholar]
  • 14.Janson CH, Tehrani MJ, Mellstedt H, Wigzell H. Anti-idiotypic monoclonal antibody to a T cell chronic lymphatic leukemia (T CLL). Characterization of the antibody, in vitro effector functions and results of therapy. Cancer Immunol Immunother. 1988;28:225. doi: 10.1007/BF00204993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Johnson W, Steplewski Z, Matthews TJ, Hamilton T, Koprowski H, Adams D. Cytolytic interaction between murine macrophages, tumor cells and monoclonal antibodies: characterization of lytic condition and requirements for effector activation. J Immunol. 1986;136:4704. [PubMed] [Google Scholar]
  • 16.Lindemalm C, Mellstedt H, Biberfeld P, Björkholm M, Christensson B, Holm G, Johansson B, Sundblad R. Blood and lymph node T lymphocyte subsets in non-Hodgkin lymphomas. Scand J Haematol. 1983;30:68. doi: 10.1111/j.1600-0609.1983.tb00636.x. [DOI] [PubMed] [Google Scholar]
  • 17.Lubeck M, Steplewski Z, Baglia F, Klein M, Dorrington K, Koprowski H. The interaction of murine IgG subclass proteind with human monocyte Fc receptors. J Immunol. 1985;135:1300. [PubMed] [Google Scholar]
  • 18.Lundgren G, Zubrowski CHF, Möller G. Differential effects of human granulocytes and lymphocytes on human fibroblasts. Clin Exp Immunol. 1986;3:817. [PMC free article] [PubMed] [Google Scholar]
  • 19.Masucci G, Lindemalm C, Frödin J-E, Hagström B, Mellstedt H. Effect of human blood mononuclear cell populations in antibody dependent cellular cytotoxicity (ADCC) using two murine (CO17-1A and Br55-2) and one chimeric (17-1A) monoclonal antibodies against a human colorectal carcinoma cell line (SW948) Hybridoma. 1988;7:429. doi: 10.1089/hyb.1988.7.429. [DOI] [PubMed] [Google Scholar]
  • 20.Mellstedt H, Holm G. In vitro studies of lymphocytes from patients with plasma cell myeloma. Clin Exp Immunol. 1973;15:309. [PMC free article] [PubMed] [Google Scholar]
  • 21.Mellstedt H, Frödin J-E, Ragnhammar P, Masucci G, Shetye J, Christensson B, Biberfeld P, Makower J, Pihlstedt P, Cedermark B, Harmenberg U, Wahren B, Rieger Å, Magnusson I, Nathansson J, Erwald R. The clinical use of monoclonal antibodies, mAb 17-1A, in the treatment of patients with metastatic colorectal carcinoma. Med Oncol Tumor Pharmacother. 1989;6:99. doi: 10.1007/BF02985230. [DOI] [PubMed] [Google Scholar]
  • 22.Metcalf D. The molecular biology and functions of granulocyte-macrophage colony stimulating factors. Blood. 1986;67:257. [PubMed] [Google Scholar]
  • 23.Mizel SB. Interleukin 1 and T-cell activation. Immunol Today. 1987;8:330. doi: 10.1016/0167-5699(87)90006-5. [DOI] [PubMed] [Google Scholar]
  • 24.Morstyn G, Lieschke G, Cebon J, Maher D, Villeval JL, Duhrsen U, McGrath K, Boyd A, O'Connor M, Nicola NA, Green M, Sheridan W, Methcalf D, Fox R, Rallings M, Spiegel R, Bonnem E (1988) Phase I study of bacterial synthesized human granulocyte-macrophage colony-stimulating factor. Abstr XII Congr Int Soc Hematol, Milan, Italy, August 28-September 3
  • 25.Ortaldo J, Woodhouse C, Morgan AC, Herberman R, Cheresh D, Reisfeld R. Analysis of effector cells in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies. J Immunol. 1987;138:3566. [PubMed] [Google Scholar]
  • 26.Santoli D, Clark SC, Kreider BL, Maslin PA, Rovera G (1988) Amplification of IL-2-driven T cell proliferation by recombinant human IL-3 and granulocyte-macrophage colony-stimulating factor. 141:519 [PubMed]
  • 27.Schulz G, Stafficeno LK, Reisfeld RA, Dennent G. Erradication of established human melanoma tumor in nude mice by antibody-directed effector cells. J Exp Med. 1985;161:1315. doi: 10.1084/jem.161.6.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Shetye J, Frödin J-E, Christensson B, Grant C, Jacobsson B, Sundelius S, Sylvén M, Biberfeld P, Mellstedt H. Immunohistochemical monitoring of metastatic colorectal carcinoma in patients treated with monoclonal antibodies (MAb 17-1A) Cancer Immunol Immunother. 1988;27:154. doi: 10.1007/BF00200021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Silberstein DS, Owen WF, Gasson JC, DiPerisio JF, Golde DW, Bina JC, Sobermann R, Austen KF, David JR. Enhancement of human eosinophil cytotoxicity and leukotrine synthesis by biosynthetic (recombinant) granulocytemacrophage colony-stimulating factor. J Immunol. 1986;137:3290. [PubMed] [Google Scholar]
  • 30.Steplewski Z, Herlyn D, Lubeck M, Kimoto Y, Herlyn M, Koprowski H. Mechanism of tumor growth inhibition. Hybridoma. 1986;5:59. [PubMed] [Google Scholar]
  • 31.Valtieri M, Santoli D, Caracciolo D, Kreider BL, Altman SW, Tweardy DJ, Gemperlein I, Mavilio F, Lange B, Rovera G. Establishment and characterization of an undifferentiated human T leukemia cell line which requires granulocyte-macrophage colony stimulatory factor for growth. J Immunol. 1987;138:4042. [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES