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

Vaccines
Martin J CannonSwetha Gujja

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.

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Citations

Jul 7, 2015·Vaccine·X CastellsaguéS S Kaplan
Aug 10, 2016·Cellular Immunology·Eliza Julia Pedraza-BrindisPablo Cesar Ortiz-Lazareno
Mar 20, 2018·Technology·Renea A FaulknorFrançois Berthiaume
Dec 29, 2020·International Immunopharmacology·Peigen ChenJing Wan
May 1, 2021·Biomedicines·Melanie A KimmMoritz Wildgruber

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Methods Mentioned

BETA
xenografts
immunoprecipitation

Clinical Trials Mentioned

NCT01802320
NCT02162719
NCT01776008
NCT01283035
NCT02390843
NCT01351103
NCT01302405
NCT01606579
NCT01663857
NCT02048709

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