The evolving landscape of immunotherapy in advanced prostate cancer
The evolving landscape of immunotherapy in advanced prostate cancer
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DOI：
10.2217/imt-2019-0019
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发表时间：
2019-07-01
期刊：
影响因子：
2.8
通讯作者：
Oh, William K.
中科院分区：
文献类型：
--
作者：
Patel, Vaibhav G.;Oh, William K.
前列腺癌存在于激素对去势抵抗疾病敏感的临床连续体中。尽管在抵抗去势的环境中使用了化疗和雄激素合成抑制剂，但这仍然是一种致命的疾病。自2011年首次获得批准以来，免疫检查点阻断的出现改变了几种肿瘤的癌症治疗和生存前景；然而，对去势抵抗型前列腺癌(CRPC)的临床益处相当有限。目前，西普鲁切尔-T仍然是CRPC环境中唯一被批准的免疫方式。这种免疫耐药的存在可能是由于前列腺癌细胞免疫原性低和肿瘤微环境免疫抑制所致。本文就CRPC早期应用免疫检查点阻断和治疗性疫苗的经验作一综述。然后，我们概述了目前正在实施的克服免疫耐药的策略，以及基因组生物标记物研究，以确定可能存在更多免疫原性肿瘤的患者。最后，对新兴的免疫治疗平台进行了展望。
Prostate cancer exists in a clinical continuum of hormone-sensitive to castration-resistant disease. Despite the use of chemotherapy and androgen synthesis inhibitors in the castration-resistant setting, this remains a lethal disease. The advent of immune checkpoint blockade has changed the outlook for cancer treatment and survival for several tumors since its first approval in 2011; however, the clinical benefit in castration-resistant prostate cancer (CRPC) is rather limited. Currently, Sipuleucel-T remains the only immune modality to be approved in CRPC setting. Such immune resistance likely exists due to low immunogenicity of prostate tumor cells and an immunosuppressive tumor microenvironment. In this review, we describe the early experiences of immune checkpoint blockade and therapeutic vaccines in CRPC. We then outline strategies currently being implemented to overcome immune resistance, as well as genomic biomarker investigation to identify patients that may harbor more immunogenic tumors. At last, we preview emerging immunotherapeutic platforms.