How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer.
How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer.
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如何打开转移性前列腺癌冷免疫微环境的热度。
DOI：
10.1038/s41391-021-00340-5
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发表时间：
2021-09
影响因子：
4.8
通讯作者：
Fong L
中科院分区：
文献类型：
--
作者：
Stultz J;Fong L
晚期前列腺癌仍然是最常见和最致命的癌症之一，尽管治疗方案取得了进展。免疫疗法对大多数患者几乎没有益处，这主要是由于免疫抑制性肿瘤微环境引起固有的“冷肿瘤”。在这篇综述中，我们讨论了前列腺肿瘤微环境的免疫病理学，用免疫疗法治疗前列腺癌的策略，以及增强免疫疗法疗效的潜在方法的前景。在PubMed、Google Scholar和科克伦等数据库中检索与前列腺癌免疫学相关的文章。我们讨论了不同类型的治疗对免疫系统的影响，以及前列腺癌逃避免疫系统的潜在机制。与前列腺癌相关的肿瘤微环境是高度免疫抑制性的，这是由于（1）调节性T细胞、肿瘤相关巨噬细胞和髓源性抑制细胞（MDSC）的功能，（2）肿瘤基质细胞和成纤维细胞分泌的细胞因子环境，以及（3）通过前列腺酸性磷酸酶产生腺苷。腺苷和肿瘤生长因子β（TGF-β）都是有效的免疫抑制分子，也可以代表潜在的治疗靶点。虽然在前列腺癌中已经有许多免疫治疗试验，但这些试验中的大多数都针对单一的免疫抑制机制，导致临床疗效有限。未来的方法将需要整合改进的患者选择以及使用联合治疗来解决多种耐药机制。前列腺癌固有地产生多种免疫抑制机制，这些机制难以用任何一种免疫方法克服。增强免疫疗法的临床活性将需要多种疗法的战略组合，以解决肿瘤免疫耐药的新机制。
Advanced prostate cancer remains one of the most common and deadly cancers, despite advances in treatment options. Immunotherapy has provided little benefit to a majority of patients, largely due to the immunosuppressive tumor microenvironment that gives rise to inherently “cold tumors”. In this review, we discuss the immunopathology of the prostate tumor microenvironment, strategies for treating prostate cancer with immunotherapies, and a perspective on potential approaches to enhancing the efficacy of immunotherapies. Databases, including PubMed, Google Scholar, and Cochrane, were searched for articles relevant to the immunology of prostate cancer. We discuss the impact of different types of treatments on the immune system, and potential mechanisms through which prostate cancer evades the immune system. The tumor microenvironment associated with prostate cancer is highly immunosuppressive due to (1) the function of regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSCs), (2) the cytokine milieu secreted by tumor stromal cells and fibroblasts, and (3) the production of adenosine via prostatic acid phosphatase. Both adenosine and tumor growth factor beta (TGF-beta) serve as potent immunosuppressive molecules that could also represent potential therapeutic targets. While there have been many immunotherapy trials in prostate cancer, the majority of these trials have targeted a single immunosuppressive mechanism resulting in limited clinical efficacy. Future approaches will require the integration of improved patient selection as well as use of combination therapies to address multiple mechanisms of resistance. Prostate cancer inherently gives rise to multiple immunosuppressive mechanisms that have been difficult to overcome with any one immunotherapeutic approach. Enhancing the clinical activity of immunotherapies will require strategic combinations of multiple therapies to address the emerging mechanisms of tumor immune resistance.
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影响因子：
5.6
作者：
Eder T;Weber A;Neuwirt H;Grünbacher G;Ploner C;Klocker H;Sampson N;Eder IE
通讯作者：
Eder IE
DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S
影响因子：
2.8
作者：
Erlandsson, Ann;Carlsson, Jessica;Davidsson, Sabina
通讯作者：
Davidsson, Sabina
影响因子：
11.5
作者：
Alfaro, Carlos;Teijeira, Alvaro;Melero, Ignacio
通讯作者：
Melero, Ignacio
影响因子：
9
作者：
Cheteh EH;Augsten M;Rundqvist H;Bianchi J;Sarne V;Egevad L;Bykov VJ;Östman A;Wiman KG
通讯作者：
Wiman KG