Tumour microenvironment (TME) characterization identified prognosis and immunotherapy response in muscle-invasive bladder cancer (MIBC).

Abstract

Tumour microenvironment (TME), which consists of widely diverse immune and stromal cells and the factors that they secrete, cultivates a chronic inflammatory, immunosuppressive, and pro-angiogenic intratumoural atmosphere, which has been reported to correlate with patient outcomes and treatment efficacy. In this study, we characterized TME pattern through the "Estimation of STromal and Immune cells in MAlignant Tumours using Expression data" (ESTIMATE) algorithm and build a TME-related signature (TMERS), which is serving as an independent prognostic factor in MIBC. Moreover, we found that the TMERS was highly positive correlated with immune infiltration, the expression of immune checkpoints and high malignancy molecular subtypes such as basal, infiltrated and basal/SCC-like. The value of the TMERS in assessing the immunotherapy response was evaluated using the tumour immune dysfunction and exclusion (TIDE) algorithm and confirmed in several cohorts treated with immune checkpoint inhibitors (ICIs). Furthermore, the TMERS had a negative correlation with the tumour mutation burden (TMB), which is a potential predictive biomarker of immunotherapy response. Remarkably, combining TMERS and TMB was more effective for survival and ICI response prediction. In conclusion, we established a novel TMERS which depicts the TME pattern and acts as a robust independent prognostic factor and predictive biomarker for the response to ICIs when combined with the TMB.