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Int. J. Mol. Sci. 2013, 14(11), 22022-22041; doi:10.3390/ijms141122022
Article

Defective Generation and Maturation of Dendritic Cells from Monocytes in Colorectal Cancer Patients during the Course of Disease

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1 Laboratory of Immunology, Department of Clinical and Experimental Medicine, University of Pisa, via Roma, 67, Pisa 56126, Italy 2 Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana (AOUP), via Roma, 67, Pisa 56126, Italy 3 Department of Clinical and Experimental Medicine, Section Medical Oncology, University of Pisa, via Roma, 67, Pisa 56126, Italy 4 Department of Surgery, Molecular, Medical and Critical Area Pathology, University of Pisa, via Paradisa, 2, Pisa 56126, Italy
* Author to whom correspondence should be addressed.
Received: 14 August 2013 / Revised: 9 October 2013 / Accepted: 17 October 2013 / Published: 7 November 2013
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
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Abstract

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in Western countries. Today, the role of the host’s immune system in controlling the progression and spread of solid tumors is broadly established. Tumor immunosurveillance escape mechanisms, such as those involving dendritic cells (DCs), the most important antigen-presenting cells, are likewise recognized processes involved in cancer. The present study evaluates the ability of CRC patients to generate DCs in vitro from circulating monocytes at both pre- and post-operative timepoints; the results are correlated with the stage of disease to shed light on the systemic immune statuses of CRC patients. Our data showed that patients’ DCs had lower co-stimulatory molecule expression and were less able to present antigens to allogeneic T cells compared to healthy controls’ (HC) DCs. Furthermore altered cytokine secretion, such as increased IL-10 and reduced IL-12 and TNF-α, was observed. At the post-operative timepoints we observed a recovery of the patients’ ability to generate immature DCs, compared to HCs, but the maturational capacity remained affected. Our study conclusively highlights the persistently impaired in vitro generation of fully mature and functional DCs, which appears to be more altered during advanced stages. This work sheds light on a dendritic cell-based tumor immune escape mechanism that could be useful for the development of more effective immunotherapeutic strategies.
Keywords: monocyte-derived dendritic cells; colorectal cancer; immunosuppression monocyte-derived dendritic cells; colorectal cancer; immunosuppression
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.

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Orsini, G.; Legitimo, A.; Failli, A.; Ferrari, P.; Nicolini, A.; Spisni, R.; Miccoli, P.; Consolini, R. Defective Generation and Maturation of Dendritic Cells from Monocytes in Colorectal Cancer Patients during the Course of Disease. Int. J. Mol. Sci. 2013, 14, 22022-22041.

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