Prognostic Value of Vimentin is Associated with Immunosuppression in Metastatic Renal Cell Carcinoma

Abstract

Background: Vimentin, a classical marker for epithelial-mesenchymal transition, is closely related to cancer metastasis. However, relationship between vimentin expression in tumor and tumor infiltrating lymphocytes is unknown. Methods: We conducted this study in 231 patients with metastatic renal cell carcinoma (mRCC) to determine the potential association between vimentin and immune status. Immunohistochemical staining was used to evaluate expression of vimentin, CD8, FOXP3, PD-1, and PD-L1 in resected tumor tissues. CD8, FOXP3, PD-1, and PD-L1 level were compared between vimentin high and low expression group. Kaplan-Meier curve and Cox regression models were used for survival analysis. Findings: High expression of vimentin, stroma PD-L1, and PD-1 indicated short overall survival, while low FOXP3 Treg or high CD8 T cells infiltration indicated long overall survival. Stroma PD-L1 (P=0.030), CD8 T cells (P<0.001), and vimentin (P=0.026) were independent prognostic factors in mRCC. High vimentin expression was associated with high PD-1, PD-L1 expression and Treg cell infiltration (all P<0.001). Treg cell infiltration was positively associated with PD-L1 (P<0.001), PD-1 expression (P<0.001), and CD8 T cell infiltration (P=0.006). Interpretation: In addition to epithelial-mesenchymal transition, we revealed another possible tumor-promoting mechanism of vimentin: immunosuppression via PD-1/PD-L1. Patients with high vimentin expression may acquire potential benefit from the recently approved PD-1/PD-L1 inhibitors. However, additional validation are needed to our findings. Funding Statement: This work was supported by the National Science Foundation of China (No. 31100629 and 81472376). Declaration of Interests: The authors declare that there is no conflict of interest to disclose. Ethics Approval Statement: The study was approved by the ethics committee of Zhongshan Hospital, Fudan University and all patients signed informed consent.