IL-10 Elicits IFNγ-Dependent Tumor Immune Surveillance
2011; Cell Press; Volume: 20; Issue: 6 Linguagem: Inglês
10.1016/j.ccr.2011.11.003
ISSN1878-3686
AutoresJohn B. Mumm, Jan Emmerich, Xueqing Zhang, Ivan H. Chan, Lingling Wu, Smita Mauze, Steven Blaisdell, Beth Basham, Jie Dai, Jeff Grein, Catherine Sheppard, Kyu Hong, Collette Cutler, Scott Turner, Drake LaFace, Melanie A. Kleinschek, Michael Judo, Gulesi Ayanoglu, John L. Langowski, Danling Gu, Brittany Paporello, Erin Murphy, Venkataraman Sriram, Saraswathi Naravula, Bela Desai, Satya Medicherla, Wolfgang Seghezzi, Terrill K. McClanahan, Susan Cannon‐Carlson, Amy M. Beebe, Martin Oft,
Tópico(s)CAR-T cell therapy research
ResumoTumor 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.
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