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Vaccines 2016, 4(4), 38; doi:10.3390/vaccines4040038

Targeting Immune Regulatory Networks to Counteract Immune Suppression in Cancer

Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Mount Sinai Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Current address: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands
Author to whom correspondence should be addressed.
Academic Editor: Theresa L. Whiteside
Received: 27 July 2016 / Revised: 14 September 2016 / Accepted: 31 October 2016 / Published: 4 November 2016
(This article belongs to the Special Issue Mechanisms of Tumor Escape from Host Immunity)
View Full-Text   |   Download PDF [620 KB, uploaded 4 November 2016]   |  


The onset of cancer is unavoidably accompanied by suppression of antitumor immunity. This occurs through mechanisms ranging from the progressive accumulation of regulatory immune cells associated with chronic immune stimulation and inflammation, to the expression of immunosuppressive molecules. Some of them are being successfully exploited as therapeutic targets, with impressive clinical results achieved in patients, as in the case of immune checkpoint inhibitors. To limit immune attack, tumor cells exploit specific pathways to render the tumor microenvironment hostile for antitumor effector cells. Local acidification might, in fact, anergize activated T cells and facilitate the accumulation of immune suppressive cells. Moreover, the release of extracellular vesicles by tumor cells can condition distant immune sites contributing to the onset of systemic immune suppression. Understanding which mechanisms may be prevalent in specific cancers or disease stages, and identifying possible strategies to counterbalance would majorly contribute to improving clinical efficacy of cancer immunotherapy. Here, we intend to highlight these mechanisms, how they could be targeted and the tools that might be available in the near future to achieve this goal. View Full-Text
Keywords: immune suppression; cancer; therapy; myeloid-derived suppressor cells; regulatory T cells; extracellular vesicles; tumor acidity immune suppression; cancer; therapy; myeloid-derived suppressor cells; regulatory T cells; extracellular vesicles; tumor acidity

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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. (CC BY 4.0).

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Camisaschi, C.; Vallacchi, V.; Vergani, E.; Tazzari, M.; Ferro, S.; Tuccitto, A.; Kuchuk, O.; Shahaj, E.; Sulsenti, R.; Castelli, C.; Rodolfo, M.; Rivoltini, L.; Huber, V. Targeting Immune Regulatory Networks to Counteract Immune Suppression in Cancer. Vaccines 2016, 4, 38.

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