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PD-L1 表达和 CD8 T 细胞浸润与淋巴结阳性前列腺癌患者的临床进展相关。

PD-L1 Expression and CD8 T-cell Infiltrate are Associated with Clinical Progression in Patients with Node-positive Prostate Cancer.

机构信息

INSERM, UMR_S 1138, Cordeliers Research Center, Team Cancer, Immune Control and Escape, Paris, France; University Paris Descartes Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; UPMC University Paris 6, Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France; Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France.

Unit of Urology and URI, Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy; NET-IMPACT, IRCCS Ospedale San Raffaele, Milan, Italy.

出版信息

Eur Urol Focus. 2019 Mar;5(2):192-196. doi: 10.1016/j.euf.2017.05.013. Epub 2017 Jun 21.

Abstract

Prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy are at higher risk of tumor recurrence and receive immediate androgen deprivation therapy (ADT). While approximately 30% of these patients do not experience recurrence, others experience disease recurrence despite ADT, and currently no biomarkers can accurately identify them. We analyzed tumors from 51 patients with node-positive prostate cancer using immunohistochemistry to investigate whether expression of the immune checkpoint ligand PD-L1 by tumor cells or the density of CD8 or CD20 cells are associated with clinical progression. Patients with at least 1% PD-L1 tumor cells had shorter metastasis-free survival than those with PD-L1 tumors (p=0.008, log-rank test). Univariate Cox regression showed that patients with PD-L1 tumors had almost four times the risk of experiencing distant metastases than those with PD-L1 tumors (hazard ratio 3.90). In addition, we found that PD-L1 expression was significantly associated with CD8 T-cell density, but not with CD20 B-cell density. While these results need to be confirmed in larger studies, they show that PD-L1 and CD8 may be used as biomarkers for node-positive patients at high risk of progression. The study also provides a rationale for selecting patients with node-positive PCa who might benefit the most from adjuvant immunotherapies. PATIENT SUMMARY: None of the available biomarkers can identify node-positive prostate cancer that will recur after surgery. We found that expression of PD-L1 by tumor cells and a high density of CD8 T cells in tumor are associated with a higher risk of clinical progression in men with node-positive prostate cancer.

摘要

前列腺癌(PCa)患者在根治性前列腺切除术后发生淋巴结侵犯,复发风险较高,需要立即接受雄激素剥夺治疗(ADT)。虽然大约 30%的患者不会复发,但其他患者尽管接受了 ADT 仍会出现疾病复发,目前尚无生物标志物可以准确识别这些患者。我们使用免疫组织化学分析了 51 例淋巴结阳性前列腺癌患者的肿瘤,以研究肿瘤细胞中免疫检查点配体 PD-L1的表达或 CD8 或 CD20 细胞的密度是否与临床进展相关。至少有 1%的 PD-L1 肿瘤细胞的患者比 PD-L1 肿瘤患者的无转移生存时间更短(p=0.008,对数秩检验)。单因素 Cox 回归显示,PD-L1 肿瘤患者发生远处转移的风险几乎是 PD-L1 肿瘤患者的四倍(危险比 3.90)。此外,我们发现 PD-L1 表达与 CD8 T 细胞密度显著相关,但与 CD20 B 细胞密度无关。虽然这些结果需要在更大的研究中得到证实,但它们表明 PD-L1 和 CD8 可作为淋巴结阳性患者进展风险较高的生物标志物。该研究还为选择可能从辅助免疫治疗中获益最大的淋巴结阳性 PCa 患者提供了依据。

患者总结

目前尚无可用的生物标志物可以识别手术后会复发的淋巴结阳性前列腺癌。我们发现,肿瘤细胞中 PD-L1 的表达和肿瘤中 CD8 T 细胞的高密度与淋巴结阳性前列腺癌患者临床进展风险较高相关。

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