Moeckel Jennifer, Staiger Nina, Mackensen Andreas, Meidenbauer Norbert, Ullrich Evelyn
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.
Oncol Lett. 2017 Jul;14(1):1089-1096. doi: 10.3892/ol.2017.6187. Epub 2017 May 17.
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.
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。