Antimetastatic and Antitumor Activities of Interleukin 10 in a Murine Model of Breast Cancer

Abstract

Based on the recent observation of others that IL-10 has little toxicity when administered systemically to human volunteers and also on the findings of this study that it has antitumor and antimetastitic properties in mice, possible use of IL-10 in the treatment of human metastatic cancers deserves consideration.

IL-10 stimulatory effects on human NK cells explored by gene profile analysis

“…[4][5][6] However, a large body of evidence in different animal tumor models opposes this theory, showing that IL-10 can favor immune-mediated cancer rejection. [7][8][9][10][11][12][13][14] In humans, the knowledge on IL-10's role in tumor immunology is scarce. In the search for a cytokine pattern that could predict tumor response to IL-2/peptide-based melanoma patient vaccination, 15 we studied cytokine mRNA abundance in fine-needle aspirate material from metastatic lesions by using quantitative real-time PCR.…”

“…Some authors have suggested that the IL-10 antitumor activity observed in animal models might be mediated by NK cells. 12,20 NK cell in vitro cytotoxicity has been reported to be enhanced by IL-10. 3,7,[21][22][23] However, IL-10 also inhibits the production of IFNg and tumor necrosis factor alpha (TNFa) by NK cells 24,25 and downregulates NK cell target molecules on tumor cells, 26 thus potentially reducing NK cell antitumor effects.…”

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

“…[5][6][7] In addition, IL10 may render tumor cells completely resistant to CTL lysis through a mechanism involving HLA I down-regulation. 8 In spite of the evidence that IL-10 has Th1-immunosuppressive and antiinflammatory effects, it has been demonstrated that the ectopic expression of IL-10 in murine B16 melanoma, 9 and in two murine models of mammary tumors 10,11 may induce the loss of tumorigenicity mainly through an NK cell-dependent mechanism. The involvement of NK was suggested to be the result of MHC class I down-regulation.…”

Keratoacanthomas have an immunosuppressive cytokine environment of increased IL-10 and decreased GM-CSF compared to squamous cell carcinomas

“…In murine models, IL-10 is capable of inducing effective anti-tumoural immune responses in vivo and inhibiting metastatic growth (Kundu et al, 1996).…”