Lin Zhiyuan, Liu Li, Xia Yu, Chen Xiang, Xiong Ying, Qu Yang, Wang Jiajun, Bai Qi, Guo Jianming, Xu Jiejie
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai China.
Oncoimmunology. 2018 Aug 6;7(10):e1477461. doi: 10.1080/2162402X.2018.1477461. eCollection 2018.
The objective response rate (ORR) of tyrosine kinase inhibitors (TKIs) therapy in metastatic renal cell cancer (mRCC) patients was not satisfactory. Effective indicator of mRCC patient selection for TKI therapy is urgently needed. The function of tumor infiltrating B lymphocytes (TIBs) in tumor immune elimination is still unclear. We aim to investigate the prognostic and predictive value of TIBs for TKI therapy in mRCC patients in this study. 108 eligible patients treated with TKI were enrolled in this study. TIBs was estimated by immunohistochemical staining of CD19 in the resected tumor, and its relationship with clinicopathological features, clinical outcomes and CD8 tumor infiltrating T lymphocytes (CD8 TILs) were evaluated. Associations between the expression level of CD19 and CD8 TILs associated cytotoxic effectors were also assessed in public databases. Results showed TIBs positive infiltration predicted better therapeutic response to sunitinib (p = 0.006), longer overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p = 0.028) in mRCC patients. Combining TIBs and International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) model showed a better predict value of OS in TKI-treated mRCC patients than IMDC model alone. We also found a positive correlation between TIBs and CD8 TILs (p < 0.001). Patients with both cells high infiltration showed markedly better OS compared with those infiltrated by CD8 T cells alone (p = 0.015). To conclude, TIBs density was not only an independent prognostic factor for mRCC patients, but also a predictive marker for TKI therapy response. It may potently enhance the antitumor effect by recruiting and activating CD8 TILs in mRCC.
酪氨酸激酶抑制剂（TKIs）治疗转移性肾细胞癌（mRCC）患者的客观缓解率（ORR）并不理想。迫切需要mRCC患者TKI治疗有效的选择指标。肿瘤浸润B淋巴细胞（TIBs）在肿瘤免疫清除中的作用仍不清楚。本研究旨在探讨TIBs对mRCC患者TKI治疗的预后和预测价值。本研究纳入了108例接受TKI治疗的符合条件的患者。通过对切除肿瘤中CD19进行免疫组化染色评估TIBs，并评估其与临床病理特征、临床结局及CD8肿瘤浸润性T淋巴细胞（CD8 TILs）的关系。还在公共数据库中评估了CD19表达水平与CD8 TILs相关细胞毒性效应器之间的关联。结果显示，TIBs阳性浸润预示mRCC患者对舒尼替尼的治疗反应更好（p = 0.006），总生存期（OS）更长（p < 0.001），无进展生存期（PFS）更长（p = 0.028）。将TIBs与国际转移性肾细胞癌数据库联盟（IMDC）模型相结合，在接受TKI治疗的mRCC患者中，其对OS的预测价值优于单独的IMDC模型。我们还发现TIBs与CD8 TILs之间存在正相关（p < 0.001）。与仅由CD8 T细胞浸润的患者相比，两种细胞均高浸润的患者OS明显更好（p = 0.015）。总之，TIBs密度不仅是mRCC患者的独立预后因素，也是TKI治疗反应的预测标志物。它可能通过招募和激活mRCC中的CD8 TILs有力地增强抗肿瘤作用。
