Abstract 548: Characterization of myeloid cells in bladder cancer

Abstract

Abstract Both cancer-associated inflammation and tumor-mediated immune suppression have been linked with expansion of myeloid cells in multiple tumor types, including bladder [1]. We previously observed a predominance of M2-like macrophages in mouse bladder tumors [2]. However, little is known about the characteristics of these myeloid cells in human bladder cancer. In this study, we analyzed myeloid cells from tumor tissues collected from patients with muscle-invasive bladder cancer. We used flow cytometry to characterize the different subsets of these myeloid cells.Myeloid cells were identified in the bladder tissue. Our results showed that bladder cancer patients have two major CD11b+CD33+ myeloid derived suppressor cell subsets: granulocyte-type HLADR−CD15+ cells and monocyte-type HLADR+CD14+ cells. Analysis of CD45+ CD11b+cells demonstrated that bladder tumors are dominated by phenotypical M2-like (CD163+ CD80lo) CD163+ M2 macrophages. The primary treatment modality for bladder cancer is Bacillus Calmete-Guerin (BCG), a live attenuated mycobacterium that is instilled into the bladder via a urethral catheter [3]. This agent remains one of the most effective immune therapies to date. However, though it is effective in prevention of tumor recurrence, response is heterogeneous and tumor recurrence is observed in up to 50% of patients over time. The predominance of immunosuppressive myeloid cells subsets among TILs in human bladder cancer suggests myeloid cells could be potential targets for therapeutic intervention in bladder cancer. We investigated the role of macrophages in BCG therapy in the MB49 bladder cancer model. Depletion of macrophages by liposomal clodronate (LC) during MB49 tumor challenge resulted in decreased tumor growth compared to BCG monotherapy suggesting that macrophages have a critical role in BCG immunotherapy. This study characterizes these myeloid populations in bladder cancer patients and also investigates their potential role in bladder cancer development and therapeutic response.