Abstract
Simple SummaryThe tumor microenvironment (TME) is considered to play a key role in the development of many types of tumors. Muscle invasive bladder cancer (MIBC), which is well known for its heterogeneity, has a highly complex TME. Herein, we integrated mass cytometry and imaging mass cytometry to systematically investigate the complexity of the MIBC TME. Our investigation revealed tumor and immune cells with diverse phenotypes. We identified a specific cancer stem-like cell cluster (ALDH+PD-L1+ER-β−), which is associated with poor prognosis and highlighted the importance of the spatial distribution patterns of MIBC TME components. The present study comprehensively elucidated the complexity of the MIBC TME and provides potentially valuable information for future research.Muscle invasive bladder cancer (MIBC) is a malignancy with considerable heterogeneity. The MIBC tumor microenvironment (TME) is highly complex, comprising diverse phenotypes and spatial architectures. The complexity of the MIBC TME must be characterized to provide potential targets for precision therapy. Herein, an integrated combination of mass cytometry and imaging mass cytometry was used to analyze tumor cells, immune cells, and TME spatial characteristics of 44 MIBC patients. We detected tumor and immune cell clusters with abnormal phenotypes. In particular, we identified a previously overlooked cancer stem-like cell cluster (ALDH+PD-L1+ER-β−) that was strongly associated with poor prognosis. We elucidated the different spatial architectures of immune cells (excluded, infiltrated, and deserted) and tumor-associated collagens (curved, stretched, directionally distributed, and chaotic) in the MIBC TME. The present study is the first to provide in-depth insight into the complexity of the MIBC TME at the single-cell level. Our results will improve the general understanding of the heterogeneous characteristics of MIBC, potentially facilitating patient stratification and personalized therapy.
Highlights
Muscle invasive bladder cancer (MIBC) is a highly aggressive malignancy, and the ninth leading cause of cancer-related deaths worldwide
We integrated CyTOF and imaging mass cytometry (IMC) to explore the complexity of the MIBC tumor microenvironment (TME)
We revealed the abnormal phenotypes of tumor epithelial cells and immune cells in the MIBC TME, and highlighted the complexity of the TME
Summary
Muscle invasive bladder cancer (MIBC) is a highly aggressive malignancy, and the ninth leading cause of cancer-related deaths worldwide. It is associated with a 40–60% survival rate at 5 years [1,2]. Plasticity enables tumor cells to constantly convert between differentiated states and cancer stem cell (CSC) states [10]. This allows them to adjust to ever-changing microenvironments, evade immune attack, invade and disseminate [11]. An immunosuppressive TME promotes immune evasion, and is associated with a poor prognosis It recruits abundant exhausted T cells and regulatory T cells (Tregs). Analyses of various cancers have shown that T cell exhaustion and Tregs drive tumor progression [14,16]
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