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      T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

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          Abstract

          The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs) while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

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          Most cited references130

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          Cancer immunotherapy: moving beyond current vaccines.

          Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on surrogate endpoints than on clinical tumor regression. In our cancer vaccine trials of 440 patients, the objective response rate was low (2.6%), and comparable to the results obtained by others. We consider here results in cancer vaccine trials and highlight alternate strategies that mediate cancer regression in preclinical and clinical models.
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            A function for interleukin 2 in Foxp3-expressing regulatory T cells.

            Regulatory T cells (T(reg) cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most T(reg) cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in T(reg) cell biology has remained controversial. To directly assess the effect of IL-2 signaling on T(reg) cell development and function, we analyzed mice containing the Foxp3(gfp) knock-in allele that were genetically deficient in either IL-2 (Il2(-/-)) or CD25 (Il2ra(-/-)). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of T(reg) cells. Unexpectedly, Il2(-/-) and Il2ra(-/-) T(reg) cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg(-/-) mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of T(reg) cells in vivo.
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              Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

              The Lancet, 374(9686), 301-314
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                Author and article information

                Journal
                Clin Dev Immunol
                CDI
                Clinical and Developmental Immunology
                Hindawi Publishing Corporation
                1740-2522
                1740-2530
                2010
                27 December 2010
                : 2010
                : 236378
                Affiliations
                1Department of Otolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany
                2Fondazione Humanitas per la Ricerca, 20089 Rozzano, Italy
                3Department of Otolaryngology, Head and Neck Surgery, Universität Essen, 45147 Essen, Germany
                4Department of Gynecology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin and Campus Mitte, 12200 Berlin, Germany
                Author notes

                Academic Editor: Eiji Matsuura

                Article
                10.1155/2010/236378
                3017942
                21234340
                1ef0ebae-9e28-4cf2-bc73-478e4dde62fe
                Copyright © 2010 A. E. Albers et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 July 2010
                : 16 October 2010
                Categories
                Review Article

                Immunology
                Immunology

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