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GM‐CSF‐transduced B16 melanoma cells are highly susceptible to lysis by normal murine macrophages and poorly tumorigenic in immune‐compromised mice
Author(s) -
Kumar Rakesh,
Yoneda Junya,
Fidler Isaiah J.,
Dong Zhongyun
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.65.1.102
Subject(s) - biology , immune system , melanoma , immunology , cancer research , macrophage , lysis , in vitro , genetics
Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF)‐transduced B16‐F10 murine melanoma cells had lower tumorigenicity in both syngeneic and nude mice than parental or Lac Z‐transduced (control) cells. The subcutaneous (s.c.) tumors producing GM‐CSF were densely infiltrated with macrophages, whereas the control tumors were not. In vitro studies showed that GM‐CSF‐transduced B16 cells were susceptible to lysis mediated by nonactivated murine macrophages, whereas control B16 cells were not. Macrophage‐mediated cytotoxicity against GM‐CSF‐transduced B16 cells was independent of the presence of NO, H 2 O 2 , O 2 ‐ , tumor necrosis factor α, and matrix metalloproteinase. Coculture experiments using GM‐CSF‐producing and ‐nonproducing B16 cells demonstrated that GM‐CSF produced by the transduced B16 cells activated macrophages to kill the bystander non‐GM‐CSF‐producing tumor cells. The results suggest that GM‐CSF released by tumor cells can induce macrophage‐mediated cytotoxicity, which in turn can inhibit the in vivo growth of GM‐CSF‐transduced tumor cells. J. Leukoc. Biol. 65: 102–108; 1999.