Prognostic and immunotherapeutic significance of tumor- infiltrating M2 macrophages in muscle-invasive bladder cancer

Muscle-invasive bladder cancer can be successfully treated by immunotherapy, however, the objective response rates are quite low. The present study aimed to explore the prognostic and immunotherapeutic effects of M2 macrophages on the subtypes of muscle-invasive bladder cancer. Tumor-infiltration levels of 22 cell types were calculated by CIBERSORT, and the survival analysis was performed to investigate the prognostic effects of 22 tumor-infiltrated cells. Statistical analysis was performed to investigate the infiltrating variance of M2 macrophages and the expression differences of immune checkpoint inhibitors in different MIBC subtypes. The correlations among M2 macrophages, immune checkpoint inhibitors, tumor mutation burden (TMB) were explored by Pearson correlation analysis. As a result, M2 macrophages significantly correlated with unfavorable survival, high tumor grade, high pathological stage, and high TNM stage system. Although immune checkpoint inhibitor and M2 macrophages expressed higher in the basal subtype of MIBC, M2 macrophages are not statistically correlated with immune checkpoint inhibitors and tumor mutation burden, apart from HAVCR2. The significant associations between macrophages M2 and outcome only for the basal squamous subtype of MIBC were observed. Overall, these findings suggested tumor infiltrating M2 macrophages as a possible prognostic marker in MIBC, especially in its basal squamous subtype, and as a potential immunotherapy target in MIBC, independent from immune checkpoint inhibitors and TMB.