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前列腺癌的免疫疗法:障碍与希望的新视野

Immunotherapy in prostate cancer: new horizon of hurdles and hopes.

作者信息

Tsaur Igor, Brandt Maximilian P, Juengel Eva, Manceau Cécile, Ploussard Guillaume

机构信息

Department of Urology and Pediatric Urology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany.

Department of Urology, CHU-Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.

出版信息

World J Urol. 2021 May;39(5):1387-1403. doi: 10.1007/s00345-020-03497-1. Epub 2020 Oct 26.

Abstract

PURPOSE

Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches such as second generation androgen receptor targeted therapies, metastatic disease is still fatal. In PCa, immunotherapy (IT) has not reached a therapeutic breakthrough as compared to several other solid tumors yet. We aimed at highlighting the underlying cellular mechanisms crucial for IT in PCa and giving an update of the most essential past and ongoing clinical trials in the field.

METHODS

We searched for relevant publications on molecular and cellular mechanisms involved in the PCa tumor microenvironment and response to IT as well as completed and ongoing IT studies and screened appropriate abstracts of international congresses.

RESULTS

Tumor progression and patient outcomes depend on complex cellular and molecular interactions of the tumor with the host immune system, driven rather dormant in case of PCa. Sipuleucel-T and pembrolizumab are the only registered immune-oncology drugs to treat this malignancy. A plethora of studies assess combination of immunotherapy with other agents or treatment modalities like radiation therapy which might increase its antineoplastic activity. No robust and clinically relevant prognostic or predictive biomarkers have been established yet.

CONCLUSION

Despite immunosuppressive functional status of PCa microenvironment, current evidence, based on cellular and molecular conditions, encourages further research in this field.

摘要

目的

前列腺癌(PCa)是男性最常见的恶性肿瘤,也是西方世界第二大常见的癌症相关死亡原因。尽管第二代雄激素受体靶向治疗等新方法不断发展,但转移性疾病仍然是致命的。与其他几种实体瘤相比,PCa的免疫疗法(IT)尚未取得治疗突破。我们旨在强调PCa中IT至关重要的潜在细胞机制,并更新该领域最重要的既往和正在进行的临床试验。

方法

我们搜索了有关PCa肿瘤微环境和对IT反应所涉及的分子和细胞机制的相关出版物,以及已完成和正在进行的IT研究,并筛选了国际大会的合适摘要。

结果

肿瘤进展和患者预后取决于肿瘤与宿主免疫系统的复杂细胞和分子相互作用,在PCa中这种相互作用相对处于休眠状态。西妥昔单抗和派姆单抗是仅有的用于治疗这种恶性肿瘤的注册免疫肿瘤药物。大量研究评估了免疫疗法与其他药物或治疗方式(如放射治疗)的联合使用,这可能会增加其抗肿瘤活性。尚未建立强大且具有临床相关性的预后或预测生物标志物。

结论

尽管PCa微环境具有免疫抑制功能状态,但基于细胞和分子状况的当前证据鼓励在该领域进行进一步研究。

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