Interleukin-10 Ablation Promotes Tumor Development, Growth, and Metastasis
- 15 January 2012
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 72 (2), 420-429
- https://doi.org/10.1158/0008-5472.can-10-4627
Abstract
Interleukin-10 (IL-10) is a broadly acting immune inhibitory cytokine that is generally thought to support tumor growth. Here we challenge this view with evidence that genetic ablation of IL-10 in the mouse significantly heightens sensitivity to chemical carcinogenesis, growth of transplanted tumors, and formation of metastases. Tumor growth in IL-10–deficient (IL-10−/−) mice was associated with an increased level of myeloid-derived suppressor cells (MDSC) and CD4+Foxp3+ regulatory T (Treg) cells in both the tumor microenvironment and the tumor-draining lymph nodes. IL-10−/− MDSCs express high levels of MHC and IL-1, and they efficiently induced formation of Treg cells. IL-1 signaling blockade reduced tumor growth mediated by IL-10 deficiency, associated with a partial rescue of tumor infiltration and function of effector T cells and a decrease in tumor angiogenesis and tumor infiltration by Treg cells. Taken together, our findings establish that endogenous IL-10 inhibits inflammatory cytokine production and hampers the development of Treg cells and MDSCs, two key components of the immunosuppressive tumor microenvironment, thereby inhibiting tumor development, growth, and metastasis. Cancer Res; 72(2); 420–9. ©2011 AACR.Keywords
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