1. Cytolytic Activity of Effector T-lymphocytes Against Hepatocellular Carcinoma is Improved by Dendritic Cells Pulsed with Pooled Tumor Antigens.
- Author
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Chieochansin T, Thepmalee C, Grainok J, Junking M, and Yenchitsomanus PT
- Subjects
- Antigens, Neoplasm pharmacology, Apoptosis, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular therapy, Cell Line, Cell Line, Tumor, Cytotoxicity, Immunologic, Humans, Immunotherapy methods, RNA pharmacology, Antigens, Neoplasm therapeutic use, Carcinoma, Hepatocellular immunology, Dendritic Cells immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Cellular immunotherapy is a promising new therapeutic approach for hepatocellular carcinoma (HCC), which has a high recurrence rate, irrespective of the treatment administered. In this study, we attempted to improve the cytolytic activity of effector T-lymphocytes against HCC. T-lymphocytes were activated by monocyte-derived dendritic cells (DCs) pulsed with cell lysate or RNA prepared from HCC cell lines. Monocytes were activated for differentiation into DCs by treatment with the IL4 and GM-CSF. DCs were pulsed with cell lysate or RNA prepared from a single cell line or combinations of two or three HCC cell lines, and then co-cultured with autologous T-lymphocytes with the intent of creating specific cytotoxicity. We discovered that DCs pulsed with total RNA effectuated greater T-lymphocyte function than DCs pulsed with total cell lysate, as evidenced by greater cytolytic activities against HCC target cells. The percentage of Huh7, HepG2, and SNU449 cell apoptosis at effector:target ratio of 10:1 was 42.6 ± 4.5% (p = 0.01), 33.6 ± 3.1% (p = 0.007), and 21.4 ± 1.4% (p < 0.001), respectively. DCs pulsed with pools of antigens prepared from three cell lines improved the cytolytic function of effector T-lymphocytes by approximately two-fold (p < 0.001), which suggests that this approach be further developed and applied for adoptive transfer treatment of HCC.
- Published
- 2019
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