Tumor-infiltrating neutrophils predict therapeutic benefit of tyrosine kinase inhibitors in metastatic renal cell carcinoma
Tumor-infiltrating neutrophils predict therapeutic benefit of tyrosine kinase inhibitors in metastatic renal cell carcinoma
复制标题
肿瘤浸润中性粒细胞预测酪氨酸激酶抑制剂在转移性肾细胞癌中的治疗效果。
DOI：
10.1080/2162402x.2018.1515611
复制
发表时间：
2019-01-01
期刊：
影响因子：
7.2
通讯作者：
Xu, Jiejie
中科院分区：
文献类型：
--
作者：
Wang, Jiajun;Liu, Li;Xu, Jiejie
肿瘤浸润中性粒细胞（TINs）在不同的癌症类型和治疗方案中显示出不同的预测作用。在这项研究中，我们研究了它们与酪氨酸激酶抑制剂（TKIs）在转移性肾细胞癌（mRCC）中的治疗效果的相关性。回顾性纳入两个独立的数据集，包括271例接受TKIs或基于IL-2/IFN-α的免疫治疗的mRCC患者，并通过免疫组织化学检测tin。TKI组50例（45.0%）样本和免疫治疗组73例（45.6%）样本中存在TINs。TKI组TINs与较短的总生存期相关（HR, 1.776; 95%CI, 1.191-2.650; p = 0.004），而免疫治疗组TINs与较短的总生存期相关（HR, 1.074; 95%CI, 0.767-1.505; p = 0.672）。多因素Cox分析证实了tki治疗患者TINs的独立预后价值（HR, 2.078, 95%CI, 1.352-3.195; p = 0.001）。此外，TKI治疗在tins缺失患者中的生存获益优于IL-2/IFN-α免疫治疗（HR, 1.561; 95%CI, 0.927-2.629; p = 0.094）。肾细胞癌TCGA队列的数据挖掘揭示了tin在肾细胞癌中主要的免疫抑制功能。TKI组（p = 0.019）、免疫治疗组（p = 0.001）和TCGA组（p < 0.001）进一步证实了TINs与肿瘤内CD8+ T细胞的负相关。总之，TINs的存在是tki治疗的mRCC患者的一个独立的、不利的预后因素。TINs还可以预测TKIs优于IL-2/IFN-α免疫治疗的治疗效果。这些发现应在临床试验或前瞻性观察性研究的数据集中得到进一步证实。
ABSTRACT Tumor-infiltrating neutrophils (TINs) show diverse predictive effects in the context of different cancer types and therapeutic regimens. In this study we investigated their relevance with therapeutic effect of tyrosine kinase inhibitors (TKIs) in metastatic renal cell carcinoma (mRCC). Two independent datasets including 271 mRCC patients treated by TKIs or IL-2/IFN-α based immunotherapy were retrospective included, and TINs were detected by immunohistochemistry. The presence of TINs was observed in 50 (45.0%) samples of the TKI cohort and in 73 (45.6%) samples of the immunotherapy cohort. TINs were associated with shorter overall survival (HR, 1.776; 95%CI, 1.191–2.650; p = 0.004) in the TKI cohort, but not in the immunotherapy cohort (HR, 1.074; 95%CI, 0.767–1.505; p = 0.672). Multivariate Cox analysis confirmed the independent prognostic value of TINs for TKI-treated patients (HR, 2.078, 95%CI, 1.352–3.195; p = 0.001), apart from other parameters. Moreover, survival benefit of TKI therapy was superior to IL-2/IFN-α immunotherapy only among TINs-absent patients (HR, 1.561; 95%CI, 0.927–2.629; p = 0.094). Data mining in the TCGA cohort of renal cell carcinoma revealed the predominant immunosuppressive function of TINs in renal cell carcinoma. The negative correlation between TINs and intratumoral CD8+ T cells was further confirmed in the TKI cohort (p = 0.019), the immunotherapy cohort (p = 0.001) and the TCGA cohort (p < 0.001). In conclusion, the presence of TINs was an independent, unfavorable prognostic factor in TKI-treated mRCC patients. TINs could also predict therapeutic benefit of TKIs over IL-2/IFN-α immunotherapy. These findings should be further confirmed within datasets of clinical trials or prospective observational studies.