Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation

Immunology. 2002 Feb;105(2):231-43. doi: 10.1046/j.1365-2567.2002.01363.x.


The aim of this study was to investigate the mechanisms by which interleukin-10 (IL-10) induces tumour growth in a mouse-melanoma model. A B16-melanoma cell line (B16-0) was transfected with IL-10 cDNA and three clones that secreted high (B16-10), medium and low amounts of IL-10 were selected. Cell proliferation and IL-10 production were compared in vitro, and tumour growth, percentages of necrotic areas, tumour cells positive for proliferating cell nuclear antigen (PCNA), IL-10 receptor (IL-10R) and major histocompatibility complex type I (MHC-I) and II (MHC-II), as well as infiltration of macrophages, CD4+ and CD8+ lymphocytes and blood vessels were compared in vivo among IL-10-transfected and non-transfected tumours. Proliferation and tumour growth were greater for IL-10-transfected than for non-transfected cells (P < 0.001), and correlated with IL-10 concentration (r > or =0.79, P < 0.006). Percentages of tumour cells positive for PCNA and IL-10R were 4.4- and 16.7-fold higher, respectively, in B16-10 than in B16-0 tumours (P < 0.001). Macrophage distribution changed from a diffuse pattern in non-transfected (6.4 +/- 1.7%) to a peripheral pattern in IL-10-transfected (3.8 +/- 1.7%) tumours. The percentage of CD4+ lymphocytes was 7.6 times higher in B16-10 than in B16-0 tumours (P = 0.002). The expression of MHC-I molecules was present in all B16-0 tumour cells and completely negative in B16-10 tumour cells. In B16-0 tumours, 89 +/- 4% of the whole tumour area was necrotic, whereas tumours produced by B16-10 cells showed only 4.3 +/- 6% of necrotic areas. IL-10-transfected tumours had 17-fold more blood vessels than non-transfected tumours (61.8 +/- 8% versus 3.5 +/- 1.7% blood vessels/tumour; P < 0.001). All the effects induced by IL-10 were prevented in mice treated with a neutralizing anti-IL-10 monoclonal antibody. These data indicate that IL-10 could induce tumour growth in this B16-melanoma model by stimulation of tumour-cell proliferation, angiogenesis and immunosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Division / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Immune Tolerance*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Macrophages / immunology*
  • Male
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Necrosis
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / immunology*
  • Transfection
  • Tumor Cells, Cultured


  • Histocompatibility Antigens Class I
  • Interleukin-10