Identification and Validation of Stromal Immunotype Predict Survival and Benefit from Adjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer

Abstract

Purpose: This study aims to construct the stromal immunotype, which could improve the prediction of postsurgical survival and adjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC).Experimental Design: A total of 118 patients with MIBC from Shanghai Cancer Center, 140 patients with MIBC from Zhongshan Hospital, and 287 patients with MIBC from TCGA cohort were included in the study. Immune cell infiltration was evaluated by IHC staining or CIBERSORT method. Five immune features were selected out of 22 immune features to construct immunotypes based on the LASSO Cox regression model.Results: Using the LASSO model, we classified patients with MIBC into stromal immunotype A subgroup (CTL^highNK^highTreg^lowMacrophage^lowMC^low) and stromal immunotype B subgroup (CTL^lowNK^lowTreg^highMacrophage^highMC^high). Significant differences were found between immunotype A and immunotype B in the combined cohort with 5-year overall survival (OS, 76.0% vs. 44.0%; P < 0.001) and 5-year disease-free survival (DFS, 62.8% vs. 48.3%; P < 0.001). Stromal immunotype was revealed to be an independent prognostic indicator in multivariate analysis in all cohorts separately. Either OS or DFS was not improved by adjuvant chemotherapy (ACT) in pT2 stage patients or pT3+pT4 patients, but further analysis revealed that OS and disease-free was significantly improved by ACT in pT3+pT4 patients (P = 0.016 and P = 0.006, respectively). Finally, stromal immunotype A showed higher immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) expression.Conclusions: The stromal immunotypes could effectively predict survival and recurrence of MIBC. Furthermore, the immunotypes might be a practical predictive tool to identify pT3+pT4 patients who would benefit from ACT. Clin Cancer Res; 24(13); 3069-78. ©2018 AACR.