Abstract
Objective: This study evaluated the prognostic value of the newly-built Immunoscore (neo-Immunoscore) in patients with renal cell carcinoma (RCC).Methods: Eighty-two patients with RCC were enrolled in this study. Their 3- and 5-year survival rates and overall survival (OS) were evaluated. The clinicopathologic data of the 82 patients were collected and analyzed. CD3, CD4, CD8, CD45RO, Foxp3, tumor necrosis factor receptor type II (TNFR2), programmed death ligand-1 (PD-L1), CD68, programmed death-1 (PD-1), cytokeratin (CK), and indoleamine 2,3-dioxygenase (IDO) were separated into two panels and stained using multiplex fluorescent immunohistochemistry methods. An immunologic prediction model of RCC patients, the neo-Immunoscore (neo-IS), was constructed using a Cox regression model. For the prognostic prediction of RCC, the neo-IS with the immunoscore (IS) proposed by the Society for Immunotherapy of Cancer (SITC) were compared by receiver operator characteristic (ROC) curve analysis. Survivals between the neo-ISlow and neo-IShigh groups were analyzed using the Kaplan–Meier method. Multivariate Cox regression survival analysis was applied to analyze independent indicators.Results: The Cox regression model allowed the establishment of a neo-IS based on three features: CD, CD4+Foxp3+CD45RO, and CD8+PD-. Compared to that of the IS proposed by the SITC, the neo-IS obtained a better prediction. The 3- and 5-year survival rates in neo-IShigh RCC patients were significantly higher than those in neo-ISlow RCC patients (94.7 vs. 77.4%, P = 0.035 and 94.7 vs. 64.5%, P = 0.002, respectively). The OS in the neo-ISlow group was significantly shorter than that in the neo-IShigh group (73 vs. 97 months, P = 0.000). In comparisons of the neo-IS with clinical pathological factors, we found that the risk stratification and neo-IS were independent factors for the prognosis of patients with RCC. Moreover, the OS rate of neo-IShigh RCC patients with low- and intermediate- risk was higher than that of neo-ISlow patients.Conclusion: The newly-constructed IS model more precisely predicted the survival of patients with RCC and may supplement the prognostic value of risk stratification.
Highlights
As one of the major urological cancers, renal cell carcinoma (RCC), which derives from renal tubular epithelial cells, constitutes ∼3.8% of all cancers [1]
In comparisons of the neo-IS with clinical pathological factors, we found that the risk stratification and neo-IS were independent factors for the prognosis of patients with RCC
Due to the high background staining and loss of antigenicity of CD45RO and granzyme B (GZMB), Galon and other researchers proposed the use of two easy membrane stains, CD3 and CD8, both in CT and IM in the IS system proposed by the Society for Immunotherapy of Cancer (SITC) to initiate a task force to validate its use in standard clinical practice as a new approach for the classification of tumors [7]
Summary
As one of the major urological cancers, renal cell carcinoma (RCC), which derives from renal tubular epithelial cells, constitutes ∼3.8% of all cancers [1]. The conventional prognostic prediction for RCC after radical nephrectomy is based on the American Joint Committee on Cancers (AJCC) pathological tumor-nodemetastasis (TNM) classification system. Other pathological and clinical variables, including Fuhrman nuclear grade, necrosis, and Eastern Cooperative Oncology Group (ECOG) score have been implemented to improve the prognostication. Combining these tools together, the University of California Los Angeles Integrated Staging System (UISS) risk stratification provides a prognostic prediction for localized RCC [4]. Because of the complexity of the immune contexture, the immunoscore (IS), which derived from the immune contexture and based on immune cell density, has been confirmed as a simple immune classification and a clinically useful prognostic marker in cancers. Few studies have assessed the prognostic factor of the IS in RCC; our study explored the significance of the IS to predict the prognosis of patients with RCC
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