Oncotarget

Research Papers:

Prostaglandin E2 and PD-1 mediated inhibition of antitumor CTL responses in the human tumor microenvironment

Jie Miao, Xu Lu, Yuefeng Hu, Chunmei Piao, Xuan Wu, Xuesong Liu, Caiting Huang, Yue Wang, Dan Li and Jingwei Liu _

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Oncotarget. 2017; 8:89802-89810. https://doi.org/10.18632/oncotarget.21155

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Abstract

Jie Miao1,*, Xu Lu2,*, Yuefeng Hu3, Chunmei Piao4, Xuan Wu2, Xuesong Liu2, Caiting Huang2, Yue Wang2, Dan Li2 and Jingwei Liu2

1Department of Radiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

2Department of Oncology, Beijing Biohealthcare Biotechnology Co.,Ltd, Bejing, China

3Department of Interventional Therapy Center, Beijing Shunyi Distinct Hospital, Bejing, China

4Department of Oncology, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Bejing, China

*These authors contributed equally to this work

Correspondence to:

Jingwei Liu, email: ljwgirl361@163.com

Keywords: cytotoxic T lymphocytes (CTL), PGE2, PD-1, tumor microenvironment

Received: June 22, 2017     Accepted: September 08, 2017     Published: September 22, 2017

ABSTRACT

Accumulating evidence indicates that inflammation plays a critical role in cancer development; however, mechanisms of immunosuppression hinder productive anti-tumor immunity to limit immunopathology. Tumor-specific cytotoxic T lymphocyte (CTL) dysfunction or exhaustion by upregulating inhibitory receptors such as programmed cell death 1 (PD-1) in tumor-bearing hosts is one such mechanism. Identification and blockade of the pathways that induce CTL dysfunction has been shown to partially restore CTL function in tumor-bearing hosts. Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme for prostanoid biosynthesis, including prostaglandin E2 (PGE2), and plays a key role in both inflammation and cancer. The disruption of COX2/PGE2 signaling using COX2 inhibitors or PGE2 receptors EP2 and EP4 antagonists, combined with anti-PD-1 blockade was therapeutic in terms of improving eradication of tumors and augmenting the numbers of functional tumor-specific CTLs. Thus, COX2/PGE2 axis inhibition is a promising adjunct therapy to PD-1 blockade for immune-based therapies in cancer.


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