Tumor infiltrating CD19 + B lymphocytes predict prognostic and therapeutic benefits in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

Oncoimmunology. 2018 Aug 6;7(10):e1477461. doi: 10.1080/2162402X.2018.1477461. eCollection 2018.

Abstract

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.

Keywords: biomarkers; renal cell carcinoma; survival; tumor infiltrating B lymphocyte; tyrosine kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

Grant support

This work was supported by the National Natural Science Foundation of China (NSFC) [81472227, 81472376, 31770851, 81702496, 81702497, 81702805 and 81772696];Zhongshan Hospital Talented Youth Program [2017ZSYQ26];Zhongshan Hospital Science Foundation [2016ZSQN30 and 2017ZSQN18];Shanghai Health and Family Planning Commission [20174Y0042];