A combination of ssGSEA and mass cytometry identifies immune microenvironment in muscle-invasive bladder cancer

J Clin Lab Anal. 2021 May;35(5):e23754. doi: 10.1002/jcla.23754. Epub 2021 Apr 4.

Abstract

Background: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with varying clinical courses and responses to treatment. To improve the prognosis of patients, it is necessary to understand such heterogeneity.

Methods: We used single-sample gene set enrichment analysis to classify 35 MIBC cases into immunity-high and immunity-low groups. Bioinformatics analyses were conducted to compare the differences between these groups. Eventually, single-cell mass cytometry (CyTOF) was used to compare the characteristics of the immune microenvironment between the patients in the two groups.

Results: Compared with patients in the immunity-low group, patients in the immunity-high group had a higher number of tumor-infiltrating immune cells and greater enrichment of gene sets associated with antitumor immune activity. Furthermore, positive immune response-related pathways were more enriched in the immunity-high group. We identified 26 immune cell subsets, including cytotoxic T cells (Tcs), helper T cells (Ths), regulatory T cells (Tregs), B cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs) using CyTOF. Furthermore, there was a higher proportion of CD45+ lymphocytes and enrichment of one Tc subset in the immunity-high group. Additionally, M2 macrophages were highly enriched in the immunity-low group. Finally, there was higher expression of PD-1 and Tim-3 on Tregs as well as a higher proportion of PD-1+ Tregs in the immunity-low group than in the immunity-high group.

Conclusion: In summary, the immune microenvironments of the immunity-high and immunity-low groups of patients with MIBC are heterogeneous. Specifically, immune suppression was observed in the immune microenvironment of the patients in the immunity-low group.

Keywords: immune microenvironment; mass cytometry; muscle-invasive bladder cancer; ssGSEA; tumor heterogeneity.

MeSH terms

  • Flow Cytometry*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunophenotyping
  • Immunosuppression Therapy
  • Muscles / pathology*
  • Neoplasm Invasiveness
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / immunology*