Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages |
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Authors: | Sica A Saccani A Bottazzi B Polentarutti N Vecchi A van Damme J Mantovani A |
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Affiliation: | Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy. Sica@irfmn.mnegri.it |
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Abstract: | IL-12 is a central cytokine in the activation of inflammation and immunity and in the generation of Th1-type responses. Tumor-associated macrophages (TAM) from mouse and human tumors showed defective production of IL-12. Defective IL-12 production was associated with lack of p50/p65 NF-kappa B activation. TAM produced increased amounts of the immunosuppressive cytokine IL-10. Abs against IL-10 restored the defective capacity of TAM to produce IL-12. Our data suggest that during tumor growth an IL-10-dependent pathway of diversion of macrophage function can be activated into the tumor microenvironment and results in the promotion of the IL-10+ IL-12- phenotype of TAM. Blocking IL-10, as well as other immunosuppressive cytokines present in the tumor microenvironment, such as TGF-beta, may complement therapeutic strategies aimed at activating type I antitumor immune responses. |
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