ABSTRACT
PURPOSE: Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. METHODS: CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. RESULTS: The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms. CONCLUSION: The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.
ABSTRACT
Metabolic syndrome (MetS) is complex and determined by the interaction between genetic and environmental factors and their influence on obesity, insulin resistance, and related traits associated with diabetes and cardiovascular disease risk. Some dynamic markers, including adiponectin (ADIPOQ), brain-derived neurotrophic factor (BDNF), and lipoprotein lipase (LPL), are implicated in MetS; however, the influence of their genetic variants on MetS susceptibility varies in racial and ethnic groups. We investigated the association of single nucleotide polymorphism (SNP)-SNP interactions among nine SNPs in six genes with MetS's genetic predisposition in Mongolian subjects. A total of 160 patients with MetS for the case group and 144 healthy individuals for the control group were selected to participate in this study. Regression analysis of individual SNPs showed that the ADIPOQ + 45GG (odds ratio (OR) = 2.09, p = 0.011) and P+P+ of LPL PvuII (OR = 2.10, p = 0.038) carriers had an increased risk of MetS. Conversely, G allele of LPL S447X (OR = 0.45, p = 0.036) and PGC-1α 482Ser (OR = 0.26, p = 0.001) allele were estimated as protective factors, respectively. Moreover, a haplotype containing the G-P+-G combination was related to MetS. Significant loci were also related to body mass index (BMI), systolic blood pressure (SBP), serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting blood glucose (FBG), adipokines, and insulin as well as insulin resistance (p < 0.05). Our results confirm that ADIPOQ + 45T > G, LPL PvII, and PGC-1α Gly482Ser loci are associated with MetS in Mongolian subjects.
