Tumoricidal potential of human macrophages grown in vitro from blood monocytes.
Adoptive transfer of activated autologous human macrophages obtained by in vitro differentiation of monocytes in culture has successfully undergone phase I clinical trials in patients with metastatic cancer. The efficacy of these autologous macrophages in the in vivo killing of human tumors has now to be demonstrated. GM-CSF was shown to increase the number of monocytes differentiating in culture into macrophages. These were then activated with IFN gamma which was reported as the best cytokine for tumoricidal activation of macrophages. The aim of this paper was to evaluate the in vitro tumoricidal activity of macrophages grown with GM-CSF and IFN gamma. This tumoricidal function was investigated by measurement of the cytolytic (chromium-51 release assay), cytostatic (anti-proliferative activity as measured by inhibition of [3H]-thymidine incorporation in two different assays) and cytotoxic (MTT assay) activities on two tumor cells lines, U937 and K562 (respectively highly sensitive and resistant to soluble TNF alpha). Our results demonstrated that GM-CSF-grown macrophages exhibited significant cytolytic, cytotoxic and cytostatic activities on U937 cells. These were partly enhanced by IFN gamma activation. In contrast, they had no lytic and lower cytotoxic and cytostatic activities on K562 cells, and these were not modified by IFN gamma activation. Our data provide valuable information for future in vivo studies using adoptively transferred autologous macrophages.
Lopez
M
M
Inserm U76, Paris, France.
Bony
V
V
Martinache
C
C
Vincent
F
F
Chokri
M
M
Abina
M A
MA
Bernard
J
J
D019264:Adoptive Transfer; D000970:Antineoplastic Agents / Q000494:pharmacology; D002452:Cell Count; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002860:Chromium Radioisotopes; D004396:Coloring Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D002860:Chromium Radioisotopes; D004396:Coloring Agents; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C022616:thiazolyl blue; D013936:Thymidine