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

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.

Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody

“…The pumc‐91/ADM was a drug resistant cell line that was established by adding the dosage of Adriamycin. The final concentration of Adriamycin was 1.0 μg/mL . The human bladder cancer T24 cell line was obtained from the Chinese Academy of Sciences.…”

“…The final concentration of Adriamycin was 1.0 μg/mL. [23][24][25][26] The human bladder cancer T24 cell line was obtained from the Chinese Academy of Sciences. The drug resistant cell line was T24/DDP, which was established by increasing the dosage of cisplatin, and the final concentration of cisplatin was 0.6 μg/mL.…”

Targeting bladder cancer using activated T�cells armed with bispecific antibodies

“…The human bladder cancer cell line Pumc-91 was provided by the Cell Laboratory of Peking union Medical College Hospital (Beijing). The drug-resistant cell line was Pumc-91/ADM, which was established by increasing the dosage of adriamycin gradually, and the final concentration of adriamycin was 1.0 µg/ml (23)(24)(25)(26). The parental cell lines were cultured in RPMI-1640 medium supplemented with 10% heatinactivated foetal bovine serum (FBS), while drug-resistant cell lines were cultured in the above-mentioned medium with 18% FBS.…”

Dendritic Cells in Sepsis: Pathological Alterations and Therapeutic Implications

“…Elevation of GCs that accompanies sepsis protects mice from LPS-induced septic shock through the suppression of DC-derived IL-12, a cytokine that can cause the secretion of other inflammatory mediators [ 84 , 96 ]. Janus kinase 2 (Jak2) is crucial for the regulation of DC function and development [ 97 , 98 ]. Deficiency of Jak2 selectively inhibits DC-mediated innate immune response and protects mice from LPS-induced septic shock [ 99 ], suggesting that blocking the IFN-receptor signaling may avoid a deleterious immune response.…”