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Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication

Authors

  • Sergio A. Quezada,

    1. Ludwig Center for Cancer Immunotherapy, Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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  • Karl S. Peggs,

    1. Department of Haematology, UCL Cancer Institute, University College London, London, UK.
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  • Tyler R. Simpson,

    1. Ludwig Center for Cancer Immunotherapy, Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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  • James P. Allison

    1. Ludwig Center for Cancer Immunotherapy, Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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James P. Allison
Ludwig Center for Cancer Immunotherapy
Howard Hughes Medical Institute
Department of Immunology
Memorial Sloan-Kettering Cancer Center
1275 York Avenue
New York, NY 10021, USA
Tel.: +1 212 122 6971
Fax: +1 212 717 3212
e-mail: allisonj@mskcc.org

Abstract

Summary:  The continual interaction of the immune system with a developing tumor is thought to result in the establishment of a dynamic state of equilibrium. This equilibrium depends on the balance between effector and regulatory T-cell compartments. Whereas regulatory T cells can infiltrate and accumulate within tumors, effector T cells fail to efficiently do so. Furthermore, effector T cells that do infiltrate the tumor become tightly controlled by different regulatory cellular subsets and inhibitory molecules. The outcome of this balance is critical to survival, and whereas in some cases the equilibrium can rapidly result in the elimination of the transformed cells by the immune system, in many other cases the tumor manages to escape immune control. In this review, we discuss relevant work focusing on the establishment of the intratumor balance, the dynamic changes in the populations of effector and regulatory T cells within the tumor, and the role of the tumor vasculature and its activation state in the recruitment of different T-cell subsets. Finally, we also discuss work associated to the manipulation of the immune response to tumors and its impact on the infiltration, accumulation, and function of tumor-reactive lymphocytes within the tumor microenvironment.

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