Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cells.
Investig Clin Urol
; 65(3): 300-310, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38714521
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 ANDMETHODS:
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Células Dendríticas
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Antígeno B7-H1
Límite:
Animals
Idioma:
En
Año:
2024
Tipo del documento:
Article