Autocrine production of IL-10 mediates defective IL-12 production and NF-κB activation in tumor-associated macrophages

Antonio Sica, Alessandra Saccani, Barbara Bottazzi, Nadia Polentarutti, Annunciata Vecchi, Jo Van Damme, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

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-κB 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-β, may complement therapeutic strategies aimed at activating type I antitumor immune responses.

Original languageEnglish
Pages (from-to)762-767
Number of pages6
JournalJournal of Immunology
Volume164
Issue number2
Publication statusPublished - Jan 15 2000

ASJC Scopus subject areas

  • Immunology

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