Analysis Of The Characteristics Of The Immune Microenvironment Of Muscle-invasive Bladder Cancer Based On Transcriptomics And Single-cell Mass Cytometry

Objective: Muscle-invasive bladder cancer(MIBC)is a group of molecular heterogeneous diseases with different clinical course and treatment response,easy to relapse and poor clinical prognosis,which has brought a heavy burden to patients and society.This research aimed to perform immunotyping of MIBC patients through the immunotyping method of 29 gene sets scores,and accurately analyzed the characteristics of the immune microenvironment of patients in the high immune infiltration group and low immune infiltration group through singlecell mass Cytometry,and analyzed the heterogeneity of MIBC features,to provide strong theoretical support for the precise treatment of MIBC.Methods:(1)The gene expression profiles of bladder cancer and paracancer tissues in 35 MIBC patients were detected by whole transcriptome sequencing;(2)MIBC patients were divided into high immune infiltration group and low immune infiltration group by immunotyping with scores of 29 gene sets;(3)The cell structure and characteristics of the immune microenvironment of patients in high immune infiltration group and low immune infiltration group were accurately analyzed by single-cell mass Cytometry.Results:(1)Compared with the patients in the low immune infiltration group,the patients in the high immune infiltration group highly expressed infiltrating immune cells and immune activation-related genes;(2)There were 1014 genes that significantly differentially expressed in the high immune infiltration group and low immune infiltration group;(3)There were more Th cells,Tc cells,B cells,macrophages,natural killer cells and dendritic cells infiltrating in the cancer tissues than in the paracancer tissues;(4)The proportion of CD45 + cells in cancer tissues of high immune infiltration group was significantly higher than that of low immune infiltration group(74.2% vs 54.2%),the difference was statistically significant(p = 0.045),which was consistent with the results of RNA transcriptome data grouping;The average proportion of T cell subsets in cancer tissues of the high immune infiltration group was higher than that of the low immune infiltration group(67.7% vs 61.8%),while the average proportion of macrophage,natural killer cell and dendritic cell subsets was relatively lower than that of the low immune infiltration group,the proportions were 11.5% vs 7.3%,5.7% vs 4.3%,8.9% vs 5.7%;(5)Compared with the high-immunity group,the expression intensity of coinhibitory receptors in regulatory T cells of patients in the low immune infiltration group was higher.Conclusions:(1)The gene expression patterns of patients in high immune infiltration group and low immune infiltration group were different;(2)Compared with paracancer tissues,the immune microenvironment of bladder cancer tissues has changed;(3)There was heterogeneity in the immune microenvironment of patients in the high immune infiltration group and the low immune infiltration group,and the immunosuppressive ability of regulatory T cells in the low immune infiltration group was stronger than that in the high immune infiltration group.