Anticancer research · 2025
Antitumor Activity of Ex Vivo Expanded Tumor Antigen Priming Cytotoxic T Cells Against Malignant Melanoma.
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Yoon Hoe-Sun, Park Young Gyu, Cho Dae Yoen, Kim Jong-Seok, Choi Jong Gwon
Аннотация
BACKGROUND/AIM: Dendritic cells (DCs) can capture antigens from tissues and migrate to lymph nodes, where they cross-present cell-associated antigens to cluster of differentiation (CD) 8+ T cells by major histocompatibility complex (MHC) I. Cytotoxic T lymphocytes remove malignant cells through T-cell receptor recognition of specific peptides that appear on the surface of cancer cells by the MHC I/beta-2-microglobulin complex. This study aimed to investigate the antitumor activity of ex vivo expanded, tumor antigen-primed cytotoxic T cells against malignant melanoma.
MATERIALS AND METHODS: T cells were induced using DC-T cell coculture and peripheral blood mononuclear cell (PBMC) methods, with and without Melan-A/MART-1 peptide stimulation. Melan-A streptamers were used for T-cell analysis. Interferon-γ and granzyme B secretion levels were measured at 1 and 2 weeks. T-cell subtypes were analyzed, and cytotoxic activity against melanoma cells was evaluated.
RESULTS: The number of positive spots significantly increased over time. CD4+ and CD8+ T cells expanded, and CD4+ T cells were the dominant T-cell subtype. The number of tumor cells (SK-MEL-28) decreased according to the cytotoxic T lymphocyte:T ratio. Cytotoxicity was observed immediately after coculture and gradually increased over 72 h.
CONCLUSION: DCs pulsed with killed allogeneic melanoma cells effectively cross-prime cytotoxic T cells that specifically target the Melan-A antigen. Moreover, naive CD8+ T cells primed by Melan-A-loaded DCs successfully killed malignant melanoma cells, highlighting a promising strategy for adoptive immunotherapy against melanoma.
MATERIALS AND METHODS: T cells were induced using DC-T cell coculture and peripheral blood mononuclear cell (PBMC) methods, with and without Melan-A/MART-1 peptide stimulation. Melan-A streptamers were used for T-cell analysis. Interferon-γ and granzyme B secretion levels were measured at 1 and 2 weeks. T-cell subtypes were analyzed, and cytotoxic activity against melanoma cells was evaluated.
RESULTS: The number of positive spots significantly increased over time. CD4+ and CD8+ T cells expanded, and CD4+ T cells were the dominant T-cell subtype. The number of tumor cells (SK-MEL-28) decreased according to the cytotoxic T lymphocyte:T ratio. Cytotoxicity was observed immediately after coculture and gradually increased over 72 h.
CONCLUSION: DCs pulsed with killed allogeneic melanoma cells effectively cross-prime cytotoxic T cells that specifically target the Melan-A antigen. Moreover, naive CD8+ T cells primed by Melan-A-loaded DCs successfully killed malignant melanoma cells, highlighting a promising strategy for adoptive immunotherapy against melanoma.