Thu, 24 Jul 2008 23:23:37 BST CiteULike: AlfonsoVicenteSuarezs randy-noelle http://www.citeulike.org/user/AlfonsoVicenteSuarez/tag/randy-noelle CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1572795 <i></i> CD40/CD154 Interactions at the Interface of Tolerance and Immunity - Annual Review of Immunology, 22(1):307 - Abstract 2007-08-17T18:43:50-00:00 randy-noelle http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1570869 <i>Clin Cancer Res, Vol. 13, No. 2. (15 January 2007), pp. 733s-740.</i><br /><br />In patients with progressive malignancy, the natural balance between proinflammatory (Yang) and inhibitory (regulatory or Yin) immune pathways is disrupted and favors cancer-specific immune suppression. Therapy with interleukin 2 (IL-2) can mobilize immune effector cells that recognize and destroy cancer. High-dose IL-2 is the only therapy that has consistently induced complete durable remissions in patients with metastatic renal cell carcinoma (RCC) but only in a few of them. The lack of benefit in most metastatic RCC patients is likely due to the ineffective manipulation of other immune circuits critical in regulating tumor cytotoxic pathways. The limited clinical activity of IL-2, RCC vaccines, and other immune therapies to date leads us to postulate that effective clinical treatment strategies will need to simultaneously enhance proinflammatory pathways and disrupt regulatory pathways. We present preliminary studies in RCC patients to highlight the complexity of the regulatory pathways and our approach to shifting the balance of proinflammatory and regulatory immune pathways using dendritic cell-tumor lysate vaccine followed by cytokine therapy. 10.1158/1078-0432.CCR-06-2064 Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang Marc Ernstoff Todd Crocenzi John Seigne Nancy Crosby Bernard Cole Jan Fisher Jill Uhlenhake Diane Mellinger Cathy Foster Conrad Farnham Kathleen Mackay Zbigniew Szczepiorkowski Susan Webber Alan Schned Robert Harris Richard Barth John Heaney Randolph Noelle doi:10.1158/1078-0432.CCR-06-2064 Clin Cancer Res, Vol. 13, No. 2. (15 January 2007), pp. 733s-740. 2007-08-16T20:44:54-00:00 2007 Clin Cancer Res 13 2 733s 740 randy-noelle http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/808729 <i>Nature, Vol. 442, No. 7106. (20 August 2006), pp. 997-1002.</i> Mast cells are essential intermediaries in regulatory T-cell tolerance Li-Fan Lu Evan Lind David Gondek Kathy Bennett Michael Gleeson Karina Pino-Lagos Zachary Scott Anthony Coyle Jennifer Reed Jacques Van Snick Terry Strom Xin Zheng Randolph Noelle doi:10.1038/nature05010 Nature, Vol. 442, No. 7106. (20 August 2006), pp. 997-1002. 2006-08-20T19:12:35-00:00 2006 Nature 0028-0836 442 7106 997 1002 Nature Publishing Group randy-noelle http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1570867 <i>J Exp Med, Vol. 204, No. 8. (6 August 2007), pp. 1765-1774.</i><br /><br />We demonstrate that all-trans retinoic acid (RA) induces FoxP3(+) adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (alpha4beta7(+) CC chemokine receptor 9(+)) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. MJ Benson K Pino-Lagos M Rosemblatt RJ Noelle doi:10.1084/jem.20070719 J Exp Med, Vol. 204, No. 8. (6 August 2007), pp. 1765-1774. 2007-08-16T20:41:59-00:00 2007 J Exp Med 0022-1007 204 8 1765 1774 randy-noelle