图书馆订阅: Guest
Begell Digital Portal Begell 数字图书馆 电子图书 期刊 参考文献及会议录 研究收集
肿瘤形成评论综述™
SJR: 0.946 SNIP: 0.503 CiteScore™: 2

ISSN 打印: 0893-9675
ISSN 在线: 2162-6448

肿瘤形成评论综述™

DOI: 10.1615/CritRevOncog.v14.i1.40
pages 57-77

Role for the cAMP-Protein Kinase A Signaling Pathway in Suppression of Antitumor Immune Responses by Regulatory T Cells

Sheraz Yaqub
The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo; and Department of Gastroenterological Surgery, Akershus University Hospital, N-1478 Lørenskog, Norway
Kjetil Tasken
The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Norway

ABSTRACT

CD4+CD25+ regulatory T (Treg) cells are engaged in the maintenance of immunological self-tolerance and suppressive control of excessive immune responses to foreign antigens. Furthermore, Treg cells infiltrate tumor tissues and may impede immune surveillance against cancer and hamper the development of an effective antitumor immunity. Depletion of Treg cells in animal models has been demonstrated to provoke tumor immunity. Attenuation of Treg-mediated suppression is therefore an interesting strategy to enhance antitumor responses. We recently found that adaptive Treg cells express COX-2 and suppress responder T cells in a PGE2-cAMP-dependent manner, which can be reversed by COX-2 inhibitors or EP-receptor antagonists. The same mechanism also appeared to be operative in patients with colorectal cancer where treatment with COX-inhibitor or cAMP-antagonist enhanced antitumor immune responses to the same extent as depletion of Treg cells. This provides mechanism-based opportunities for pharmacological intervention to interfere with Treg immunosuppression. In this review we will discuss key mechanisms used by Treg cells to suppress antitumor immunity, with emphasis on the cAMP-PKA pathway. We will also highlight some of the roles of Treg cells in cancer.


Articles with similar content:

Natural IgM and the Development of B Cell-Mediated Autoimmune Diseases
Critical Reviews™ in Immunology, Vol.36, 2016, issue 2
Nicole Baumgarth, Trang T. T. Nguyen
T Lymphocyte Migration: The Influence of Interactions via Adhesion Molecules, the T Cell Receptor, and Cytokines
Critical Reviews™ in Immunology, Vol.15, 1995, issue 3-4
Julius Klominek, Sten-Erik Bergstrom, Dan Hauzenberger, Karl-Gosta Sundqvist
Modulation of Immune Responses by Histone Deacetylase Inhibitors
Critical Reviews™ in Oncogenesis, Vol.20, 2015, issue 1-2
Heiko Brennenstuhl, Ulrike Naumann, Sonja Schotterl
Nitric Oxide-Mediated Regulation of Cancer Immune Escape
Forum on Immunopathological Diseases and Therapeutics, Vol.1, 2010, issue 4
D. Robert Siemens, Charles H. Graham
Targeting NKG2D and NKp30 Ligands Shedding to Improve NK Cell−Based Immunotherapy
Critical Reviews™ in Immunology, Vol.36, 2016, issue 6
Marco Cippitelli, Alessandra Soriani, Alessandra Zingoni, Elisabetta Vulpis, Angela Santoni, Cinzia Fionda, Ilaria Nardone