| Literature DB >> 22172723 |
John B Mumm1, Jan Emmerich, Xueqing Zhang, Ivan Chan, Lingling Wu, Smita Mauze, Steven Blaisdell, Beth Basham, Jie Dai, Jeff Grein, Catherine Sheppard, Kyu Hong, Collette Cutler, Scott Turner, Drake LaFace, Melanie Kleinschek, Michael Judo, Gulesi Ayanoglu, John Langowski, Danling Gu, Brittany Paporello, Erin Murphy, Venkataraman Sriram, Saraswathi Naravula, Bela Desai, Satya Medicherla, Wolfgang Seghezzi, Terrill McClanahan, Susan Cannon-Carlson, Amy M Beebe, Martin Oft.
Abstract
Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8(+) T cells. Intratumoral CD8(+) T cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8(+) T cells, expression of the Th1 cytokine interferon-γ (IFNγ) and granzymes in CD8(+) T cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8(+) T cell function and controls tumor growth.Entities:
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Year: 2011 PMID： 22172723 DOI： 10.1016/j.ccr.2011.11.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743