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자료유형
학술저널
저자정보
임소연 (가톨릭관동대학교) 박준희 (가톨릭관동대학교) 장현 (가톨릭관동대학교)
저널정보
대한비뇨기과학회 Investigative and Clinical Urology Investigative and Clinical Urology Vol.64 No.1
발행연도
2023.1
수록면
74 - 81 (8page)
DOI
https://doi.org/10.4111/icu.20220031

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Purpose: Programmed cell death protein 1 (PD-1) and ligand programmed death ligand 1 (PD-L1) are important immune-suppressive regulators in the tumor microenvironment. A vaccine-induced immune effect on tumor cells is blunted by the immunosuppressive tumor microenvironment. Therefore, we hypothesized that a dendritic cell (DC) vaccine combined with anti-PD-1 (αPD-1) antibodies could elicit a synergistic anti-tumor immunity in bladder cancer. Materials and Methods: We produced a model of subcutaneous transplantation in C3H/HeJ mice by transplanting murine MBT-2 bladder cancer cells. DCs were isolated from normal C3H/HeJ mice, followed by stimulation against MBT-2 lysate before injection. Two weeks later of MBT-2 inoculation, αPD-1 and stimulated DCs were injected two times at one-week interval intraperitoneally and intravenously, respectively. Tumor-infiltrating immune cells and splenocytes were analyzed using flow cytometry. T-cell-mediated anti-tumor responses were measured by interferon (IFN)-γ ELISPOT and lactate dehydrogenase assays. Results: The mice treated with DC+αPD-1 showed a significant decrease in tumor volume compared to the DC-treated mice and IgG-treated group. Survival of the DC+αPD-1–treated group was improved compared with that of the IgG-treated mice. IFN-γ secretion from splenocytes against tumor cells was significantly increased in the DC+αPD-1 group compared with that of αPD-1–treated mice. The frequency of CD8+ and CD4+ T-cells in spleens was statistically increased in the DC+αPD-1–treated mice compared to those receiving monotherapy (DC- or αPD-1–treated group). Conclusions: Our results support the hypothesis that the combination therapy of a DC vaccine and αPD-1 antibodies could enhance the anti-tumor immune response against bladder cancer.

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