Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cellsopen access
- Authors
- Choi, Se Young; Kim, Yunlim; Lim, Bumjin; Wee, Chung Beum; Chang, In Ho; Kim, Choung-Soo
- Issue Date
- May-2024
- Publisher
- KOREAN UROLOGICAL ASSOC
- Keywords
- Dendritic cell; Immune tolerance; Immunotherapy; Prostate cancer
- Citation
- INVESTIGATIVE AND CLINICAL UROLOGY, v.65, no.3, pp 300 - 310
- Pages
- 11
- Journal Title
- INVESTIGATIVE AND CLINICAL UROLOGY
- Volume
- 65
- Number
- 3
- Start Page
- 300
- End Page
- 310
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/73779
- DOI
- 10.4111/icu.20230348
- ISSN
- 2466-0493
2466-054X
- Abstract
- Purpose: We developed immune checkpoint molecules to target recombinant dendritic cells (DCs) and verified their anti-tumor efficacy and immune response against prostate cancer. Materials and Methods: DCs were generated from mononuclear cells in the tibia and femur bone marrow of mice. We knocked down the programmed death ligand 1 (PD-L1) on monocyte-derived DCs through siRNA PD-L1. Cell surface antigens were immune fluorescently stained through flow cytometry to analyze cultured cell phenotypes. Furthermore, we evaluated the efficacy of monocyte-derived DCs and recombinant DCs in a prostate cancer mouse model with subcutaneous TRAMP-C1 cells. Lastly, DC-induced mixed lymphocyte and lymphocyte-only proliferations were compared to determine cultured DCs'function. Results: Compared to the control group, siRNA PD-L1 therapeutic DC-treated mice exhibited significantly inhibited tumor volume and increased tumor cell apoptosis. Remarkably, this treatment substantially augmented interferon-gamma and interleukin-2 production by stimulating T-cells in an allogeneic mixed lymphocyte reaction. Moreover, we demonstrated that PD-L1 gene silencing improved cell proliferation and cytokine production. Conclusions: We developed monocyte-derived DCs transfected with PD-L1 siRNA from mouse bone marrow. Our study highlights that PD-L1 inhibition in DCs increases antigen-specific immune responses, corroborating previous immunotherapy methodology findings regarding castration-resistant prostate cancer.
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