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通过免疫检查点抑制剂时代的生物标志物发现实现个体化肾癌治疗:我们处于什么位置?

Individualizing renal cell carcinoma treatment through biomarkers discovery in the era of immune checkpoint inhibitors: where do we stand?

机构信息

Chair of Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari 'A. Moro'.

Division of Oncology, A.O.U. Consorziale Policlinico di Bari, Bari.

出版信息

Curr Opin Urol. 2021 May 1;31(3):236-241. doi: 10.1097/MOU.0000000000000870.

Abstract

PURPOSE OF REVIEW

The treatment landscape of metastatic renal cell carcinoma has greatly evolved over the past fifteen years, leading to a significant improvement in the outcome of our patients. However, there is still an urgent need for predictive biomarkers that could guide our treatment selection, especially in the present era of immune-based treatments.

RECENT FINDINGS

A number of putative biomarkers of immunotherapy activity have been proposed over the past few years, including PD-L1 immunohistochemical expression, tumor mutational burden, neoantigens load, insertions and deletions, complex gene signatures, as well as lymphocytic subpopulations (either circulating or tumor-infiltrating). However, despite preliminary intriguing findings, no biomarker for immune checkpoint activity has emerged so far, that could be used in everyday clinical practice, mainly due to preliminary, or frankly, conflicting results.

SUMMARY

The quest for an 'ideal' biomarker, which should be characterized by adequate specificity, sensibility, predictive (and not just prognostic) value, robustness, reproducibility, ease of evaluation and low cost, is still ongoing.

摘要

目的综述

在过去的十五年中,转移性肾细胞癌的治疗领域发生了巨大的变化,这使得我们的患者的预后得到了显著改善。然而,目前仍迫切需要预测性生物标志物来指导我们的治疗选择,特别是在免疫治疗时代。

最近的发现

过去几年中提出了许多免疫治疗活性的潜在生物标志物,包括 PD-L1 免疫组化表达、肿瘤突变负担、新抗原负荷、插入和缺失、复杂的基因特征以及淋巴细胞亚群(循环或肿瘤浸润)。然而,尽管有初步的有趣发现,但迄今为止,还没有出现任何可用于日常临床实践的免疫检查点活性的生物标志物,主要是因为初步的,或者坦率地说,相互矛盾的结果。

总结

对于一种“理想”的生物标志物的探索仍在继续,这种生物标志物应具有足够的特异性、敏感性、预测(而不仅仅是预后)价值、稳健性、可重复性、易于评估和低成本。

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