肾细胞癌对免疫检查点抑制剂产生耐药性与失去反应:两种不同的现象。

IF 4.6 Q1 ONCOLOGY 癌症耐药(英文) Pub Date : 2023-09-20 eCollection Date: 2023-01-01 DOI:10.20517/cdr.2023.47
Arya Mariam Roy, Saby George
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引用次数: 0

摘要

免疫检查点抑制剂(ICI)的引入彻底改变了转移性肾细胞癌(mRCC)的治疗,并显著改善了患者的预后。使用靶向PD-1/PD-L1和CTLA-4的ICIs的单一疗法或组合,以及添加ICIs和酪氨酸激酶抑制剂,显著提高了mRCC患者的总体生存率。尽管有这些有希望的结果,但仍有一部分患者对治疗没有反应(原发性耐药性)或随着时间的推移对治疗产生耐药性(获得性耐药性)。了解ICI治疗耐药性发展的机制对于mRCC的管理至关重要,因为它们可以用于确定创新治疗策略的新靶点。目前,开发新的预测和预后生物标志物的需求尚未得到满足,这些生物标志物可以帮助mRCC患者开发个性化的治疗方案。在这篇综述中,我们总结了RCC中ICI耐药性的几种机制,包括肿瘤微环境的改变、替代免疫检查点途径的上调以及遗传和表观遗传学变化。此外,我们强调了可用于克服耐药性的潜在策略,如联合治疗、靶向治疗和免疫调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Emerging resistance vs. losing response to immune check point inhibitors in renal cell carcinoma: two differing phenomena.

The introduction of immune checkpoint inhibitor (ICI) has revolutionized the treatment of metastatic renal cell carcinoma (mRCC) and has dramatically improved the outcomes of patients. The use of monotherapy or combinations of ICIs targeting PD-1/PD-L1 and CTLA-4, as well as the addition of ICIs with tyrosine kinase inhibitors, has significantly enhanced the overall survival of mRCC patients. Despite these promising results, there remains a subset of patients who either do not respond to treatment (primary resistance) or develop resistance to therapy over time (acquired resistance). Understanding the mechanisms underlying the development of resistance to ICI treatment is crucial in the management of mRCC, as they can be used to identify new targets for innovative therapeutic strategies. Currently, there is an unmet need to develop new predictive and prognostic biomarkers that can aid in the development of personalized treatment options for mRCC patients. In this review, we summarize several mechanisms of ICI resistance in RCC, including alterations in tumor microenvironment, upregulation of alternative immune checkpoint pathways, and genetic and epigenetic changes. Additionally, we highlight potential strategies that can be used to overcome resistance, such as combination therapy, targeted therapy, and immune modulation.

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