Abstract:
The involvement of the prostaglandin E2 (PGE2) system in cancer progression has long been recognized. PGE2 functions as an autocrine and paracrine signaling molecule with pleiotropic effects in the human body. High levels of intratumoral PGE2 and overexpression of the key metabolic enzymes of PGE2 have been observed and suggested to contribute to tumor progression. This has been claimed for different types of solid tumors, including, but not limited to, lung, breast, and colon cancer. PGE2 has direct effects on tumor cells and angiogenesis that are known to promote tumor development. However, one of the main mechanisms behind PGE2 driving cancerogenesis is currently thought to be anchored in suppressed antitumor immunity, thus providing possible therapeutic targets to be used in cancer immunotherapies. EP2 and EP4, two receptors for PGE2, are emerging as being the most relevant for this purpose. This review aims to summarize the known roles of PGE2 in the immune system and its functions within the tumor microenvironment. SIGNIFICANCE STATEMENT: Prostaglandin E2 (PGE2) has long been known to be a signaling molecule in cancer. Its presence in tumors has been repeatedly associated with disease progression. Elucidation of its effects on immunological components of the tumor microenvironment has highlighted the potential of PGE2 receptor antagonists in cancer treatment, particularly in combination with immune checkpoint inhibitor therapeutics. Adjuvant treatment could increase the response rates and the efficacy of immune-based therapies.
摘要:
前列腺素E2(PGE2)系统在癌症进展中的参与早已被认识到。PGE2作为自分泌和旁分泌信号分子在人体内具有多效性作用。已经观察到高水平的肿瘤内PGE2和PGE2的关键代谢酶的过表达,并且表明有助于肿瘤进展。这已被声称适用于不同类型的实体瘤,包括,但不限于,肺,乳房,还有结肠癌.PGE2对已知促进肿瘤发展的肿瘤细胞和血管生成具有直接作用。然而,PGE2驱动癌症发生的主要机制之一目前被认为是锚定在抑制的抗肿瘤免疫,从而为癌症免疫疗法提供了可能的治疗靶点。EP2和EP4(PGE2的两种受体)正在成为与此目的最相关的受体。本文旨在总结PGE2在免疫系统中的已知作用及其在肿瘤微环境中的功能。意义陈述:前列腺素E2(PGE2)长期以来被认为是癌症中的信号分子。它在肿瘤中的存在与疾病进展反复相关。阐明其对肿瘤微环境免疫成分的影响,突出了PGE2受体拮抗剂在癌症治疗中的潜力,特别是与免疫检查点抑制剂疗法组合。辅助治疗可以提高应答率和基于免疫的疗法的功效。