Tumor inflammation is prognostically significant in high-grade muscle-invasive
bladder cancer (MIBC). However, the underlying mechanisms remain elusive. To identify
inflammation-associated immune gene expression patterns, we performed transcriptomic profiling of 40 MIBC archival
tumors using the NanoString nCounter Human v.1.1 PanCancer Panel. Findings were validated using the TCGA MIBC dataset. Unsupervised and supervised clustering identified a distinctive immune-related gene expression profile for
inflammation, characterized by significant upregulation of 149 genes, particularly
chemokines, a subset of which also had potential prognostic utility. Some of the most enriched biological processes were lymphocyte activation and proliferation, leukocyte adhesion and migration, antigen processing and presentation and cellular response to IFN-γ. Upregulation of numerous IFN-γ-inducible
chemokines, class II MHC molecules and immune checkpoint genes was detected as part of the
complex immune response to MIBC. Further, B-cell markers linked to
tertiary lymphoid structures were upregulated, which in turn is predictive of
tumor response to
immunotherapy and favorable outcome. Our findings of both an overall activated immune profıle and immunosuppressive microenvironment provide novel insights into the
complex immune milieu of MIBC with
inflammation and supports its clinical significance for predicting prognosis and immunotherapeutic responsiveness, which warrants further investigation. This may open novel opportunities to identify mechanisms for developing new immunotherapeutic strategies.