CXC chemokine ligand 9/monokine induced by IFN-gamma production by tumor cells is critical for T cell-mediated suppression of cutaneous tumors.
The role of tumor-produced chemokines in the growth of malignancies remains poorly understood. We retrieved an in vivo growing MCA205 fibrosarcoma and isolated tumor cell clones that produce both CXCL9/monokine induced by IFN-gamma (Mig) and CXCL10/IFN-gamma-inducible protein 10 following stimulation with IFN-gamma and clones that produce IFN-gamma-inducible protein 10 but not Mig. The Mig-deficient variants grew more aggressively as cutaneous tumors in wild-type mice than the Mig-producing tumor cells. The growth of Mig-expressing, but not Mig-deficient, tumor cells was suppressed by NK and T cell activity. Transduction of Mig-negative variants to generate constitutive tumor cell production of Mig resulted in T cell-dependent rejection of the tumors and in induction of protective tumor-specific CD8(+) T cell responses to Mig-deficient tumors. The results indicate a critical role for tumor-derived Mig in T cell-mediated responses to cutaneous fibrosarcomas and suggest the loss of Mig expression as a mechanism used by tumor cells to evade these responses.
Gorbachev
Anton V
AV
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA. gorbaca@ccf.org
Kobayashi
Hirohito
H
Kudo
Daisuke
D
Tannenbaum
Charles S
CS
Finke
James H
JH
Shu
Suyu
S
Farber
Joshua M
JM
Fairchild
Robert L
RL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D005354:Fibrosarcoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015846:Monokines / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C485969:Cxcl9 protein, mouse; D015846:Monokines; D009363:Neoplasm Proteins; D007371:Interferon-gamma