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髓源性抑制细胞作为前列腺癌的关键参与者和有前景的治疗靶点

Myeloid-Derived Suppressor Cells as Key Players and Promising Therapy Targets in Prostate Cancer.

作者信息

Siemińska Izabela, Baran Jarek

机构信息

Department of Clinical Immunology, Jagiellonian University Medical College, Cracow, Poland.

University Centre of Veterinary Medicine, Jagiellonian University - University of Agriculture, Cracow, Poland.

出版信息

Front Oncol. 2022 Jul 4;12:862416. doi: 10.3389/fonc.2022.862416. eCollection 2022.

Abstract

Prostate cancer (PC) is the second most often diagnosed malignancy in men and one of the major causes of cancer death worldwide. Despite genetic predispositions, environmental factors, including a high-fat diet, obesity, a sedentary lifestyle, infections of the prostate, and exposure to chemicals or ionizing radiation, play a crucial role in PC development. Moreover, due to a lack of, or insufficient T-cell infiltration and its immunosuppressive microenvironment, PC is frequently classified as a "cold" tumor. This is related to the absence of tumor-associated antigens, the lack of T-cell activation and their homing into the tumor bed, and the presence of immunological cells with regulatory functions, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and tumor-associated macrophages (TAMs). All of them, by a variety of means, hamper anti-tumor immune response in the tumor microenvironment (TME), stimulating tumor growth and the formation of metastases. Therefore, they emerge as potential anti-cancer therapy targets. This article is focused on the function and role of MDSCs in the initiation and progression of PC. Clinical trials directly targeting this cell population or affecting its biological functions, thus limiting its pro-tumorigenic activity, are also presented.

摘要

前列腺癌(PC)是男性中第二常见的诊断出的恶性肿瘤,也是全球癌症死亡的主要原因之一。尽管存在遗传易感性,但环境因素,包括高脂肪饮食、肥胖、久坐不动的生活方式、前列腺感染以及接触化学物质或电离辐射,在前列腺癌的发展中起着关键作用。此外,由于缺乏或T细胞浸润不足及其免疫抑制微环境,前列腺癌常被归类为“冷”肿瘤。这与肿瘤相关抗原的缺失、T细胞激活的缺乏及其归巢到肿瘤床以及具有调节功能的免疫细胞的存在有关,包括髓源性抑制细胞(MDSC)、调节性T细胞(Treg)和肿瘤相关巨噬细胞(TAM)。它们全部通过多种方式阻碍肿瘤微环境(TME)中的抗肿瘤免疫反应,刺激肿瘤生长和转移的形成。因此,它们成为潜在的抗癌治疗靶点。本文重点关注MDSC在前列腺癌发生和进展中的功能和作用。还介绍了直接靶向该细胞群体或影响其生物学功能从而限制其促肿瘤活性的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/116f/9289201/7afaf19a8d4a/fonc-12-862416-g001.jpg

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