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Sunitinib does not impair natural killer cell function in patients with renal cell carcinoma.舒尼替尼不会损害肾细胞癌患者的自然杀伤细胞功能。
Oncol Lett. 2017 Jul;14(1):1089-1096. doi: 10.3892/ol.2017.6187. Epub 2017 May 17.
2
The kinase inhibitors sunitinib and sorafenib differentially affect NK cell antitumor reactivity in vitro.激酶抑制剂舒尼替尼和索拉非尼在体外对 NK 细胞抗肿瘤反应有不同的影响。
J Immunol. 2009 Dec 15;183(12):8286-94. doi: 10.4049/jimmunol.0902404.
3
Metastatic Renal Cell Carcinoma Rapidly Progressive to Sunitinib: What to Do Next?转移性肾细胞癌快速进展至舒尼替尼:下一步该怎么办?
Eur Urol Oncol. 2021 Apr;4(2):274-281. doi: 10.1016/j.euo.2019.06.018. Epub 2019 Jul 20.
4
Impact of Clinicopathological Features on Survival in Patients Treated with First-line Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Renal Cell Carcinoma: A Meta-analysis of Randomized Clinical Trials.一线免疫检查点抑制剂联合酪氨酸激酶抑制剂治疗肾细胞癌患者的生存与临床病理特征的关系:一项随机临床试验的荟萃分析。
Eur Urol Focus. 2022 Mar;8(2):514-521. doi: 10.1016/j.euf.2021.03.001. Epub 2021 Mar 11.
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Mutated Von Hippel-Lindau-renal cell carcinoma (RCC) promotes patients specific natural killer (NK) cytotoxicity.突变型 von Hippel-Lindau-肾细胞癌 (RCC) 可促进患者特异性自然杀伤 (NK) 细胞的细胞毒性。
J Exp Clin Cancer Res. 2018 Dec 4;37(1):297. doi: 10.1186/s13046-018-0952-7.
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[Effect of Sunitinib therapy on immune function of patients with advanced renal cell carcinoma].[舒尼替尼治疗对晚期肾细胞癌患者免疫功能的影响]
Zhonghua Wai Ke Za Zhi. 2016 Oct 1;54(10):741-745. doi: 10.3760/cma.j.issn.0529-5815.2016.10.004.
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Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK cells during expansion and thereby enhances effector functions in a dose- and time-dependent manner.索拉非尼在扩增过程中反常地激活多克隆人 NK 细胞中的 RAS/RAF/ERK 通路,从而以剂量和时间依赖的方式增强效应功能。
Clin Exp Immunol. 2018 Jul;193(1):64-72. doi: 10.1111/cei.13128. Epub 2018 May 7.
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Nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial.纳武利尤单抗、纳武利尤单抗-伊匹木单抗和VEGFR酪氨酸激酶抑制剂作为转移性透明细胞肾细胞癌的一线治疗(BIONIKK):一项生物标志物驱动、开放标签、非对照、随机2期试验。
Lancet Oncol. 2022 May;23(5):612-624. doi: 10.1016/S1470-2045(22)00128-0. Epub 2022 Apr 4.
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Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma.曲美替尼增强肾细胞癌对抗血管生成酪氨酸激酶抑制剂反应的临床前证据。
Mol Cancer Ther. 2016 Jan;15(1):172-83. doi: 10.1158/1535-7163.MCT-15-0170. Epub 2015 Oct 20.
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PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma.PTEN 参与肾细胞癌对舒尼替尼和索拉非尼的耐药。
Anticancer Res. 2020 Apr;40(4):1943-1951. doi: 10.21873/anticanres.14149.

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NK Cell-Based Immunotherapy in Renal Cell Carcinoma.基于自然杀伤细胞的免疫疗法在肾癌中的应用
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2
An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors.利用肿瘤移植体剖析肾细胞癌肿瘤微环境的实证方法确定了与预后炎症因子缺失的联系。
Cancer Discov. 2018 Sep;8(9):1142-1155. doi: 10.1158/2159-8290.CD-17-1246. Epub 2018 Jun 8.

本文引用的文献

1
EAU guidelines on renal cell carcinoma: 2014 update.EAU 指南:肾细胞癌. 2014 年更新版.
Eur Urol. 2015 May;67(5):913-24. doi: 10.1016/j.eururo.2015.01.005. Epub 2015 Jan 21.
2
International variations and trends in renal cell carcinoma incidence and mortality.国际上肾细胞癌发病率和死亡率的变化和趋势。
Eur Urol. 2015 Mar;67(3):519-30. doi: 10.1016/j.eururo.2014.10.002. Epub 2014 Oct 16.
3
Dosing patterns, toxicity, and outcomes in patients treated with first-line sunitinib for advanced renal cell carcinoma in community-based practices.在社区实践中,一线使用舒尼替尼治疗晚期肾细胞癌患者的给药模式、毒性及治疗结果。
Clin Genitourin Cancer. 2014 Dec;12(6):413-21. doi: 10.1016/j.clgc.2014.06.015. Epub 2014 Jun 21.
4
Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI) in solid cancers: a review of clinical trials.舒尼替尼作为多靶点酪氨酸激酶抑制剂(TKI)在实体癌中的临床反应:临床试验综述
Onco Targets Ther. 2014 May 12;7:719-28. doi: 10.2147/OTT.S61388. eCollection 2014.
5
Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity.理解肾细胞癌的病理变异:从生物学复杂性中提炼治疗机会。
Eur Urol. 2015 Jan;67(1):85-97. doi: 10.1016/j.eururo.2014.04.029. Epub 2014 May 21.
6
Improving outcomes in metastatic clear cell renal cell carcinoma by sequencing therapy.通过测序指导治疗改善转移性透明细胞肾细胞癌的治疗效果。
Am Soc Clin Oncol Educ Book. 2014:e228-38. doi: 10.14694/EdBook_AM.2014.34.e228.
7
Nilotinib combined with interleukin-2 mediates antitumor and immunological effects in a B16 melanoma model.尼罗替尼联合白细胞介素-2在B16黑色素瘤模型中介导抗肿瘤和免疫效应。
Oncol Rep. 2014 May;31(5):2015-20. doi: 10.3892/or.2014.3070. Epub 2014 Mar 10.
8
Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines.细胞因子治疗进展后接受舒尼替尼和索拉非尼治疗的转移性肾细胞癌患者的临床和实验室预后因素
Urol Oncol. 2014 May;32(4):488-95. doi: 10.1016/j.urolonc.2013.09.011. Epub 2013 Dec 8.
9
Small molecule targeted therapies for the second-line treatment for metastatic renal cell carcinoma: a systematic review and indirect comparison of safety and efficacy.小分子靶向治疗转移性肾细胞癌二线治疗:系统评价和安全性及疗效的间接比较。
J Cancer Res Clin Oncol. 2013 Nov;139(11):1917-26. doi: 10.1007/s00432-013-1510-5. Epub 2013 Sep 14.
10
Risk factors for renal cell carcinoma in the VITAL study.VITAL 研究中的肾癌风险因素。
J Urol. 2013 Nov;190(5):1657-61. doi: 10.1016/j.juro.2013.04.130. Epub 2013 May 9.

舒尼替尼不会损害肾细胞癌患者的自然杀伤细胞功能。

Sunitinib does not impair natural killer cell function in patients with renal cell carcinoma.

作者信息

Moeckel Jennifer, Staiger Nina, Mackensen Andreas, Meidenbauer Norbert, Ullrich Evelyn

机构信息

Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany.

LOEWE Center for Cell and Gene Therapy, Goethe University Frankfurt, D-60590 Frankfurt, Germany.

出版信息

Oncol Lett. 2017 Jul;14(1):1089-1096. doi: 10.3892/ol.2017.6187. Epub 2017 May 17.

DOI:10.3892/ol.2017.6187
PMID:28693278
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5494766/
Abstract

Although the available treatment options have expanded, the survival of patients with metastatic renal cell carcinoma (RCC) remains poor. As patients with RCC lack responsiveness to chemotherapy or radiation, therapeutic options predominantly include surgical interventions and immunomodulatory approaches, including the administration of tyrosine kinase inhibitors (TKIs) such as sunitinib. Natural killer (NK) cells have been reported to be key players in TKI-mediated off-target effects on the immune system. However, only limited information is available regarding the possible impact of sunitinib on the function of NK cells of individual patients. The present study reports on the immunomonitoring results of three patients with metastatic RCC who underwent sunitinib treatment. These results were compared with age-matched, healthy controls in terms of the immune status of T, B and NK cells, focusing on functional analyses of NK cells. In all three patients, NK cell number, subset distribution and function, as measured by cluster of differentiation 107a degranulation, did not exhibit any significant alterations as a result of sunitinib treatment. These results indicate that sunitinib does not negatively affect NK cell function, which supports the pursuit of therapeutic modalities that combine immunomodulation and NK cell-stimulating approaches.

摘要

尽管可用的治疗选择有所增加,但转移性肾细胞癌(RCC)患者的生存率仍然很低。由于RCC患者对化疗或放疗缺乏反应,治疗选择主要包括手术干预和免疫调节方法,包括给予酪氨酸激酶抑制剂(TKIs),如舒尼替尼。据报道,自然杀伤(NK)细胞是TKI介导的对免疫系统脱靶效应的关键参与者。然而,关于舒尼替尼对个体患者NK细胞功能可能产生的影响,目前只有有限的信息。本研究报告了三名接受舒尼替尼治疗的转移性RCC患者的免疫监测结果。将这些结果与年龄匹配的健康对照在T、B和NK细胞免疫状态方面进行比较,重点是NK细胞的功能分析。在所有三名患者中,通过分化簇107a脱颗粒测量的NK细胞数量、亚群分布和功能,并未因舒尼替尼治疗而出现任何显著变化。这些结果表明,舒尼替尼不会对NK细胞功能产生负面影响,这支持了探索将免疫调节和NK细胞刺激方法相结合的治疗模式。