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Vaccines 2015, 3(2), 448-466; doi:10.3390/vaccines3020448

Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

1
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA
2
Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Mary Lenora (Nora) Disis
Received: 16 April 2015 / Revised: 24 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
(This article belongs to the Special Issue Cancer Vaccines)
View Full-Text   |   Download PDF [423 KB, uploaded 29 May 2015]   |  

Abstract

The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines. View Full-Text
Keywords: ovarian cancer; macrophages; dendritic cells; regulatory T cells; indoleamine 2,3-dioxygenase; aryl hydrocarbon receptor; c-KIT; STAT3 ovarian cancer; macrophages; dendritic cells; regulatory T cells; indoleamine 2,3-dioxygenase; aryl hydrocarbon receptor; c-KIT; STAT3
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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Cannon, M.J.; Ghosh, D.; Gujja, S. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages. Vaccines 2015, 3, 448-466.

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