ABSTRACT
Serum levels of soluble MHC class I-related chain A (sMICA) are related with the prognosis of various types of cancer; however, few studies on the prognostic value of sMICA in hepatocellular carcinoma (HCC) have been reported. In this study, we retrospectively investigated the relationship between sMICA levels and clinical features of advanced HCC, and we assessed the prognostic value of sMICA in advanced HCC. Furthermore, the relationship of serum sMICA levels and natural killer group 2, member D (NKG2D) expression on natural killer (NK) cells was also evaluated. We detected sMICA levels in the serum of 60 advanced HCC patients using enzyme-linked immunosorbent assay (ELISA) and measured expression levels of NKG2D on NK cells using flow cytometry. We found that serum sMICA levels in HCC patients were in the range of 0.10-6.21 ng/mL. Chi-square analyses showed that sMICA level was significantly related with only tumor size. Survival analysis showed that a high sMICA level was significantly related with poor prognosis among HCC patients. Multivariate analyses indicated that sMICA was an independent prognostic factor. In addition, the levels of CD56+NKG2D+ NK cells were within the range of 11.2%-55.4%, and correlation analyses indicated that sMICA level was negatively correlated with the level of NKG2D+ NK cells. Our results suggest that serum sMICA levels may be an independent prognostic factor for advanced HCC.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , Blood , Allergy and Immunology , Pathology , Histocompatibility Antigens Class I , Blood , Killer Cells, Natural , Allergy and Immunology , Metabolism , Liver Neoplasms , Blood , Allergy and Immunology , Pathology , Multivariate Analysis , NK Cell Lectin-Like Receptor Subfamily K , Metabolism , Neoplasm Staging , Retrospective Studies , Survival Rate , Tumor BurdenABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>Cytokine-induced killer (CIK) cells and autologous dendritic cells-CIK (DC-CIK) cells co-cultured with autologous dendritic cells (DCs) and CIK cells are commonly used for immunotherapy recently. We compared the anti-tumor immune response of CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach.</p><p><b>METHODS</b>Peripheral monocytes were isolated from patients with renal carcinoma, lung cancer, or maxillary squamous cell carcinoma and their healthy adult children. Isolated cells were cultured and induced as DCs and CIK cells in vitro. CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively, generating DC-CIK cells and semi-allogeneic DC-CIK cells. The anti-tumor activities of autologous CIK cells, autologous DC-CIK cells, and semi-allogeneic DC-CIK cells were measured by LDH assay. Intracellular staining was used to test the secretion of cytokines. Flow cytometry was applied for detecting the phonotype changes of these three types of cells. Cell proliferation and cell apoptosis were detected by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and Annexin V/PI respectively.</p><p><b>RESULTS</b>Compared with autologous CIK cells and DC-CIK cells, semi-allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN-gamma secretion, reduced IL-4 secretion, increased the ratio of CD3(+)CD56(+) cells and CD3(+)CD8(+) cells, decreased the number of CD4(+)CD25(+) cells, promoted cell proliferation, and lessened cell apoptosis.</p><p><b>CONCLUSIONS</b>Semi-allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells. Our results provided experimental evidence for clinical application of DC-CIK cells.</p>