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阴茎癌的免疫治疗

英文原题:Immune-based therapies in penile cancer.

查看英文原题

Immune-based therapies in penile cancer.

PubMed 2022/07/18(内容时间) Nat Rev Urol Q1 · IF 13.6(JCR 2025)

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中文摘要

阴茎癌是一种罕见的泌尿生殖系统恶性肿瘤,预后差且治疗选择极为有限,用于治疗具有高风险特征的局限性病变或晚期病变时通常无法治愈。为满足对更有效治疗方式的未满足需求,免疫检查点阻断、人乳头瘤病毒(HPV)导向疫苗和过继性T细胞疗法等免疫基础疗法已成为晚期阴茎癌的潜在治疗选择。多种免疫细胞如细胞毒性T淋巴细胞(CTLs)、肿瘤相关巨噬细胞和髓源性抑制细胞已被证实可浸润阴茎癌肿瘤,且与HPV阴性肿瘤相比,HPV阳性肿瘤表现出不同的免疫景观。研究结果还证明了肿瘤相关巨噬细胞等免疫细胞、程序性死亡配体-1等免疫标志物以及HPV状态在阴茎癌中的预后价值。

综上所述,这些发现强调了肿瘤免疫微环境作为预后指标来源和免疫基础疗法潜在治疗靶点的临床相关性。目前关于免疫基础疗法在阴茎癌中安全性和有效性的证据有限,但基于其他恶性肿瘤(包括其他鳞状细胞癌)研究中有希望的结果,多项临床和临床前研究正在评估这些疗法在该疾病中的应用。

此外,还存在将免疫基础疗法与现有系统性治疗方案相结合的机会,以期为晚期阴茎癌患者提供最大获益。未来的工作应侧重于扩展用于免疫基础药物发现的临床前模型。

展开英文摘要原文

Penile cancer is a rare genitourinary malignancy that is associated with poor outcomes and severely limited therapeutic options that are generally non-curative when used to treat localized disease with high-risk features or advanced disease. To address the unmet need for treatment modalities with increased effectiveness, immune-based therapies such as immune-checkpoint blockade, human papilloma virus (HPV)-directed vaccines and adoptive T cell therapies have emerged as potential treatment options for advanced penile cancer. A diverse array of immune cells such as cytotoxic T lymphocytes (CTLs), tumour-associated macrophages and myeloid-derived suppressor cells have been shown to infiltrate penile cancer tumours, with distinct immune landscapes being demonstrated in HPV-positive compared with HPV-negative tumours.

Study results have also demonstrated the prognostic value of immune cells such as tumour-associated macrophages, immune markers such as programmed death ligand-1, and HPV-status in penile cancer. Taken together, these findings underscore the clinical relevance of the tumour immune microenvironment as a source of both prognostic indicators and potential therapeutic targets for immune-based therapies.

Current evidence regarding the safety and efficacy of immune-based therapies is limited in penile cancer, but a number of clinical and preclinical studies are ongoing to evaluate these therapies in this disease based on promising results from studies in other malignancies, including other squamous cell carcinomas.

In addition, an opportunity exists to combine immune-based therapies with existing lines of systemic therapy to offer the most benefit to patients with advanced penile cancer. Future work should focus on expansion of preclinical models for immune-based drug discovery.

论文信息

作者
Joshi VB、Spiess PE、Necchi A、Pettaway CA、Chahoud J
第一作者单位
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.United States
通讯作者单位
Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. jad.chahoud@moffitt.org.United States
文献类型
综述
期刊
Nature reviews. Urology2022 Aug
原文标识
PubMed 35851333 · DOI 10.1038/s41585-022-00617-x