title: Interleukin-10 ablation promotes tumor development, growth, and metastasis.
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.
authors: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors: Takashi
authors: T
authors: Tanikawa
authors: Cailin Moira
authors: CM
authors: Wilke
authors: Ilona
authors: I
authors: Kryczek
authors: Grace Y
authors: GY
authors: Chen
authors: John
authors: J
authors: Kao
authors: Gabriel
authors: G
authors: Núñez
authors: Weiping
authors: W
authors: Zou
mesh_terms: D000818:Animals; D001397:Azoxymethane; D048708:Cell Growth Processes / Q000276:immunology; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10; D001397:Azoxymethane