Pu Dan, Yin Liyuan, Huang Lin, Qin Changlong, Zhou Yuwen, Wu Qiang, Li Yan, Zhou Qinghua, Li Lu
Department of Lung Cancer Center, Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Oncology Department, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2021 Feb 26;11:637504. doi: 10.3389/fonc.2021.637504. eCollection 2021.
The clinical application of immunotherapy is the milestone of cancer treatment. However, some patients have bad reaction. Cyclooxygenase-2 (COX-2) is frequently expressed in multiple cancer cells and is associated with poor prognosis. It is the key enzyme of prostaglandin E (PGE2) that has been proved to promote the development, proliferation and metastasis of tumor cells. Recent studies further find the PGE2 in tumor microenvironment (TME) actively triggers tumor immune evasion many ways, leading to poor response of immunotherapy. COX-2 inhibitor is suggested to restrain the immunosuppression of PGE2 and may enhance or reverse the response of immune checkpoint inhibitors (ICIs). This review provides insight into the mechanism of COX-2/PGE2 signal in immunosuppressive TME and summarizes the clinical application and trials in cancer treatment.
免疫疗法的临床应用是癌症治疗的里程碑。然而，一些患者会出现不良反应。环氧合酶-2（COX-2）在多种癌细胞中频繁表达，且与预后不良相关。它是前列腺素E（PGE2）的关键酶，已被证明可促进肿瘤细胞的发展、增殖和转移。最近的研究进一步发现，肿瘤微环境（TME）中的PGE2通过多种方式积极触发肿瘤免疫逃逸，导致免疫疗法反应不佳。建议使用COX-2抑制剂抑制PGE2的免疫抑制作用，并可能增强或逆转免疫检查点抑制剂（ICIs）的反应。本文综述深入探讨了COX-2/PGE2信号在免疫抑制性TME中的作用机制，并总结了其在癌症治疗中的临床应用和试验情况。
