Abstract 3093: Prognostic value of novel immune basal subtypes in muscle invasive bladder cancer

Abstract

Abstract Using gene expression profiling we previously reported the existence of 3 molecular subtypes (basal, p53-like and luminal) characterized by distinct gene expression patterns and clinical outcomes in muscle-invasive bladder cancer (MIBC). Among the subtypes, basal tumors were associated with advanced stage at presentation and shorter survival in the absence of neoadjuvant chemotherapy (NAC). Our recent analysis identified two novel immune subtypes within the basal tumors (basal immune signature enriched - “BIE” and basal immune signature suppressed - “BIS”) using immune infiltration markers that are known to have prognostic value in multiple solid tumors. The analysis revealed that BIE had significantly improved survival outcomes while BIS was associated with the worst survival outcomes among all subtypes in TCGA MIBC data (n=408). Survival outcomes in BIE tumors were validated in an independent cohort (GSE48075, p <0.05). The characterization of the immune landscape in our novel subtypes using TCGA’s recent pan-cancer immunogenomics data showed that the BIE subtype was significantly enriched with ‘INF -γ dominant’ immune subtype out of the 6 TCGA immune subtypes (wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet and TGF-β dominant, p < 0.05). Since immune activation has been associated with response to chemotherapy in other tumor types, we explored the potential significance of the novel immune subtypes using public data consisting of patients who received NAC followed by radical cystectomy (GSE52219 and GSE69795). In these cohorts, chemotherapy was active as measured by pathological downstaging rates (≤ pT1 at cystectomy). Based on pathological downstaging, BIE was the most responsive to chemotherapy while BIS and p53-like tumors were resistant to chemotherapy (p < 0.05). We also used the recently developed CIBERSORT tool to estimate stromal cell infiltration in the NAC cohort. The results predicted that the BIE subtype was highly enriched with CD8+ T cells and NK cells (p <0.001). Taken together, our results reveal the existence of novel immune subtypes within basal tumors with distinct molecular features and survival outcomes in MIBC. The clinical implications of these subtypes will be further evaluated. Citation Format: Woonyoung Choi, Debasish Sundi, I-ling Lee, Arlene Siefker-Radtke, Colin Dinney, Bogdan Czerniak, Seungchan Kim, David McConkey. Prognostic value of novel immune basal subtypes in muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3093.