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      Cytokines in Cancer Immunotherapy

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          Abstract

          Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system to eradicate cancer has been accompanied by heightened efforts to characterize cytokines and exploit their vast signaling networks to develop cancer treatments. The goal of this paper is to review the major cytokines involved in cancer immunotherapy and discuss their basic biology and clinical applications. The paper will also describe new cytokines in pre-clinical development, combinations of biological agents, novel delivery mechanisms, and potential directions for future investigation using cytokines.

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          Most cited references189

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          IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity.

          Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice do not completely lack functional T cells and that two components of the immune system-IFNgamma and perforin-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFNgamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.
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            The nature of the principal type 1 interferon-producing cells in human blood.

            Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
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              The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design.

              Interleukin-2 and interleukin-15 have pivotal roles in the control of the life and death of lymphocytes. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin-2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin-15 is dedicated to the prolonged maintenance of memory T-cell responses to invading pathogens. As discussed in this Review, the biology of these cytokines will affect the development of novel therapies for malignancy and autoimmune diseases, as well as the design of vaccines against infectious diseases.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                Cancers
                Cancers
                Molecular Diversity Preservation International (MDPI)
                2072-6694
                December 2011
                13 October 2011
                : 3
                : 4
                : 3856-3893
                Affiliations
                [1 ] Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA; E-Mail: smlee@ 123456fhcrc.org
                [2 ] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: kmargoli@ 123456seattlecca.org ; Tel.: +1-206-288-7565; Fax: +1-206-288-6681.
                Article
                cancers-03-03856
                10.3390/cancers3043856
                3763400
                24213115
                6816362d-c5ab-43db-a2b6-655b4e3c8c53
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/)

                History
                : 16 August 2011
                : 24 September 2011
                : 27 September 2011
                Categories
                Review

                cytokines,cancer,immunotherapy,interleukin-2,interferon
                cytokines, cancer, immunotherapy, interleukin-2, interferon

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