Thu, 24 Jul 2008 23:23:05 BST CiteULike: AlfonsoVicenteSuarezs Colombo http://www.citeulike.org/user/AlfonsoVicenteSuarez/author/Colombo CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1688016 <i>J. Exp. Med., Vol. 196, No. 4. (19 August 2002), pp. 541-549.</i><br /><br />Progressing tumors in man and mouse are often infiltrated by dendritic cells (DCs). Deficient antitumor immunity could be related to a lack of tumor-associated antigen (TAA) presentation by tumor-infiltrating DCs (TIDCs) or to a functional defect of TIDCs. Here we investigated the phenotype and function of TIDCs in transplantable and transgenic mouse tumor models. Although TIDCs could encompass various known DC subsets, most had an immature phenotype. We observed that TIDCs were able to present TAA in the context of major histocompatibility complex class I but that they were refractory to stimulation with the combination of lipopolysaccharide, interferon gamma, and anti-CD40 antibody. We could revert TIDC paralysis, however, by in vitro or in vivo stimulation with the combination of a CpG immunostimulatory sequence and an anti-interleukin 10 receptor (IL-10R) antibody. CpG or anti-IL-10R alone were inactive in TIDCs, whereas CpG triggered activation in normal DCs. In particular, CpG plus anti-IL-10R enhanced the TAA-specific immune response and triggered de novo IL-12 production. Subsequently, CpG plus anti-IL-10R treatment showed robust antitumor therapeutic activity exceeding by far that of CpG alone, and elicited antitumor immune memory. 10.1084/jem.20020732 Reversal of Tumor-induced Dendritic Cell Paralysis by CpG Immunostimulatory Oligonucleotide and Anti-Interleukin 10 Receptor Antibody Alain Vicari Claudia Chiodoni Celine Vaure Smina Ait-Yahia Christophe Dercamp Fabien Matsos Olivier Reynard Catherine Taverne Philippe Merle Mario Colombo Anne O'Garra Giorgio Trinchieri Christophe Caux doi:10.1084/jem.20020732 J. Exp. Med., Vol. 196, No. 4. (19 August 2002), pp. 541-549. 2007-09-23T22:45:31-00:00 2002 J. Exp. Med. 196 4 541 549 tolerogenic-dcs tumor-dcs http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1387964 <i>Cytokine & Growth Factor Reviews, Vol. 13, No. 2. (April 2002), pp. 155-168.</i><br /><br />Interleukin-12 (IL-12) has an essential role in the interaction between the innate and adaptive arms of immunity by regulating inflammatory responses, innate resistance to infection, and adaptive immunity. Endogenous IL-12 is required for resistance to many pathogens and to transplantable and chemically induced tumors. In experimental tumor models, recombinant IL-12 treatment has a dramatic anti-tumor effect on transplantable tumors, on chemically induced tumors, and in tumors arising spontaneously in genetically modified mice. IL-12 utilizes effector mechanisms of both innate resistance and adaptive immunity to mediate anti-tumor resistance. IFN-[gamma] and a cascade of other secondary and tertiary pro-inflammatory cytokines induced by IL-12 have a direct toxic effect on the tumor cells or may activate potent anti-angiogenic mechanisms. The stimulating activity of IL-12 on antigen-specific immunity relies mostly on its ability to determine or augment Th1 and cytotoxic T lymphocyte responses. Because of this ability, IL-12 has a potent adjuvant activity in cancer and other vaccines. The promising data obtained in the pre-clinical models of anti-tumor immunotherapy have raised much hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity and modest clinical response observed in the clinical trials point to the necessity to plan protocols that minimize toxicity without affecting the anti-tumor effect of IL-12. Interleukin-12 in anti-tumor immunity and immunotherapy Mario Colombo Giorgio Trinchieri Cytokine & Growth Factor Reviews, Vol. 13, No. 2. (April 2002), pp. 155-168. 2007-06-13T17:46:43-00:00 2002 Cytokine & Growth Factor Reviews 13 2 155 168 il-12-general