Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism.
Interleukin-10 (IL-10) is a recently described pleiotropic cytokine secreted mainly by type 2 helper T cells. Previous studies have shown that IL-10 suppresses cytokine expression by natural killer (NK) and type 1 T cells, thus down-regulating cell-mediated immunity and stimulating humoral responses. We here report that injected IL-10 protein is an efficient inhibitor of tumor metastasis in experimental (B16-F10) and spontaneous (M27 and Lox human melanoma) metastasis models in vivo at doses that do not have toxic effects on normal or cancer cells. Histological characterization after IL-10 treatment confirmed the absence of CD8+ and CD4+ T cells and macrophages at the sites of tumor growth, but abundant NK cells were localized at these sites. This unexpected finding was confirmed by showing that IL-10 inhibits most B16-F10 and Lox metastases in mice deficient in T or B cells (SCID and nu/nu mice), but not in those deficient in NK cells (beige mice or NK cell-depleted mice). However, IL-10 downregulation of pro-inflammatory cytokine production and/or recruitment of additional effector cells may also be involved in the anti-tumor effect at higher local concentrations of IL-10, since transfected B16 tumor cells expressing high amounts of IL-10 were rejected by normal, nu/nu, or SCID mice at the primary tumor stage, and there was still a 33% inhibition of tumor metastasis in beige mice.
Zheng
L M
LM
Tumor Biology Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Ojcius
D M
DM
Garaud
F
F
Roth
C
C
Maxwell
E
E
Li
Z
Z
Rong
H
H
Chen
J
J
Wang
X Y
XY
Catino
J J
JJ
King
I
I
D000818:Animals; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000556:secondary; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000517:prevention & control*
D016753:Interleukin-10