Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism.

Abstract

SummaryInterleukin-10 (IL-10) is a recently described pteiotropic cytokine secreted mainly by type 2 helper T cells. Previous studies have shown that IL-t0 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-t0 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-t0 downregulation of pro-inflammatory cytokine production and/or recruitment of additional eff~ctor cells may also be involved in the anti-tumor effect at higher local concentrations of IL-t0, since transfected B16 tumor cells expressing high amounts of lL-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.

Tissue Expression, Serum and Salivary Levels of IL-10 in Patients with Head and Neck Squamous Cell Carcinoma

“…These findings indicate that decreased expression of IL-10 in tumor destroys antitumor mechanisms and causes progression of the disease. In support of this hypothesis, some studies have shown that systematic prescription of IL-10 prevents metastasis in melanoma tumor cells, sarcoma and colorectal cancer (Berman et al,1996;Zheng et al,1996).…”

The Kinetics of In Vivo Priming of CD4 and CD8 T Cells by Dendritic/Tumor Fusion Cells in MUC1-Transgenic Mice

“…Traditionally, Th1 have been thought to be associated with cellmediated immunity and Th2 to be related to humoral immunity. However, both types of T cells have been shown to participate in the antitumor immune response (37)(38)(39)(40)(41)(42). The heterogeneity of cytokine profiles has been extensively demonstrated (43)(44)(45).…”

IL-10 expression by CT26 colon carcinoma cells inhibits their malignant phenotype and induces a T cell-mediated tumor rejection in the context of a systemic Th2 response

“…22 Parallel depletion studies performed with B16 cells showed no involvement of T cells confirming previous evidence indicating that NK cells were mainly responsible for tumor rejection in the B16 melanoma model. 13 The involvement of either NK or T cell subset in an antitumor response was suggested to be related to MHC class I expression by the tumor cells. Down-regulation of MHC class I levels was associated with increased NK activity.…”