Abstract
BackgroundInfiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome. However, the contribution of each subset of tumour-infiltrating immune cells is unclear. The objective of this study was to perform cell phenotyping and transcriptional profiling of the tumour immune microenvironment and analyse the association of distinct cell subsets and genes with BC prognosis.MethodsClinical data of 412 patients with BC and 433 transcription files for normal and cancer tissues were downloaded from The Cancer Genome Atlas. The CIBERSORT algorithm was used to determine the relative abundance of 22 immune cell types in each sample and the ESTIMATE algorithm was used to identify differentially expressed genes within the tumour microenvironment of BC, which were subjected to functional enrichment and protein-protein interaction (PPI) analyses. The association of cell subsets and differentially expressed genes with patient survival and clinical parameters was examined by Cox regression analysis and the Kaplan-Meier method.ResultsResting natural killer cells and activated memory CD4+ and CD8+ T cells were associated with favourable patient outcome, whereas resting memory CD4+ T cells were associated with poor outcome. Differential expression analysis revealed 1334 genes influencing both immune and stromal cell scores; of them, 97 were predictive of overall survival in patients with BC. Among the top 10 statistically significant hub genes in the PPI network, CXCL12, FN1, LCK, and CXCR4 were found to be associated with BC prognosis.ConclusionTumour-infiltrating immune cells and cancer microenvironment-related genes can affect the outcomes of patients and are likely to be important determinants of both prognosis and response to immunotherapy in BC.
Highlights
Infiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome
The correlation heat map revealed that CD8+ T cells and activated memory CD4+ T cells were negatively correlated with resting memory CD4+ T cells, whereas activated memory CD4+ T cells were positively correlated with CD8+ T cells and resting natural killer (NK) cells (Fig. 1c)
Our results showed that stromal cell scores were positively correlated with cancer stage, indicating that stromal components in the tumour microenvironment (TME) may play an important role in BC progression, which is consistent with the findings of a previous study [18]
Summary
Infiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome. The contribution of each subset of tumour-infiltrating immune cells is unclear. The objective of this study was to perform cell phenotyping and transcriptional profiling of the tumour immune microenvironment and analyse the association of distinct cell subsets and genes with BC prognosis. Among the patients with BC, approximately 25% have muscle-invasive cancer or metastatic disease and 75% have non-muscle invasive cancer (NMIBC) [2]. The tumour microenvironment (TME) surrounding cancer cells originally consists of tumour stromal cells, the extracellular matrix, and soluble molecules. The two main non-tumour components of the TME are immune cells and stromal cells.
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