Immunosuppressive effect of bladder cancer on function of dendritic cells involving of Jak2/STAT3 pathway.

Weigang Xiu,Shangyan Zhou,Man Zhang,Ting Lei,Juan Ma

doi:10.18632/oncotarget.11434

Abstract

Function of dendritic cells (DCs) is impaired by some cancer cells. However, the effect of bladder cancer cell (BCC) on phenotype and function of DCs remains unclear. In this study, healthy human peripheral blood mononuclear cells (PBMCs) derived DCs were co-cultured with BCC pumc-91 and adriamycin-resistant pumc-91/ADM. The expression of DC markers and costimulatory molecules decreased after co-culture. Co-cultured DCs rapidly underwent apoptosis, and had a declined capability to produce IL-8 and RANTES. Furthermore, co-cultured DCs showed impaired allogeneic T cell proliferation and T cell-derived cytokine secretion. Finally, AG490, a Jak2/STAT3 inhibitor, restored the expression of DC markers and costimulatory molecules. Of note, compared with control DCs, DCs co-cultured with pumc-91 produced more IP-10; DCs co-cultured with pumc-91/ADM secreted more MIG. Taken together, these results suggest BCC may inhibit maturation and function of DCs involving of Jak2/STAT3 pathway, and there may be different mechanisms by which adriamycin-resistant BCC restrains DC function in antitumor immune response.

Highlights

Bladder cancer is one of the most common malignancies of urinary system, about 429800 new cases and 165100 deaths occurring in 2012 worldwide [1]
These data indicate that bladder cancer cell, and the soluble factors from BCC inhibited the maturation of human dendritic cells (DCs), and there might be different mechanisms by which adriamycin-resistant BCC inhibits DC maturation
Immature DCs may lead to deficient activation of specific cytotoxic T cells, suppress antitumor immune response and promote cancer growth and progression [8, 10]

Summary

Introduction

Bladder cancer is one of the most common malignancies of urinary system, about 429800 new cases and 165100 deaths occurring in 2012 worldwide [1]. Bladder cancer can be categorized as non-muscle invasive bladder cancer (NMIBC) and muscleinvasive bladder cancer (MIBC). The characteristic of non-muscle invasive bladder cancer is frequent recurrence and low mortality. In the case of muscle-invasive bladder cancer, despite exist multiple treatment strategies, such as radical cystectomy, radiation therapy and chemotherapy, survival rates are poor [3]. These therapies restrict growth and development of tumor, they do not prevent recurrence and drug-resistant [4, 5].

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