PURPOSE Hepatocellular carcinoma (HCC) displays particular resistance to conventional cytostatic agents. Alternative treatment strategies focus on novel substances exhibiting antineoplastic and/or immunomodulatory activity enhancing for example natural killer (NK) cell antitumor reactivity. However, tumor-associated ligands engaging activating NK cell receptors are largely unknown. Exceptions a...

Immunoligands for stimulatory natural killer (NK)-cell receptors can be targeted to the surface of malignant cells by fusing them to antibody fragments. Mimicking an "induced-self" phenotype, such recombinant immunoligands signal danger, trigger NK-cell cytotoxicity and synergistically enhance antibody-dependent cellular cytotoxicity. These findings may be translated into novel immunotherapeuti...

Natural killer (NK) cells are known to target cancer stem cells and undifferentiated tumors. In this paper, we provide a novel strategy for expanding large numbers of super-charged NK cells with significant potential to lyse and differentiate cancer stem cells and demonstrate the differences in the dynamics of NK cell expansion between healthy donors and cancer patients. Decline in cytotoxicity...

INTRODUCTION We aimed to investigate the effect of valproic acid (VPA) on NKG2D ligand expression in human renal carcinoma cell lines and to investigate the mechanisms. MATERIAL AND METHODS Different concentrations of VPA from 0.5 mM to 8.0 mM were applied to 786-O and ACHN cell lines, respectively. Cell viability after treatment with VPA was determined by flow cytometry (FCM). Real-time PCR ...

Our previous reports demonstrated that the magnitude of natural killer (NK) cell-mediated cytotoxicity correlate directly with the stage and level of differentiation of tumor cells. In addition, we have shown previously that activated NK cells inhibit growth of cancer cells through induction of differentiation, resulting in the resistance of tumor cells to NK cell-mediated cytotoxicity through ...

Extracellular signal-regulated kinases (ERK, also known as mitogen-activated protein kinases) are serine-threonine kinases transducing signals elicited upon ligand binding to several tyrosine kinase-associated receptors. We have reported that ERK2 phosphorylation and activation follows engagement of the low affinity receptor for the Fc portion of IgG (CD16) on NK cells, and is necessary for CD1...

Viral infection of the liver is a major risk factor for hepatocellular carcinoma (HCC). Natural killer (NK) cells recognize virally infected and oncogenically transformed cells, suggesting a therapeutic role for NK-cell infusions in HCC. Using the K562-mb15-41BBL cell line as a stimulus, we obtained large numbers of activated NK cells from the peripheral blood of healthy donors. Expanded NK cel...

Non-major histocompatibility complex-restricted cytotoxicity or natural killer (NK) activity could be detected in all intestinal lamina propria mononuclear cell preparations of histologically normal mucosa from 57 patients with gastrointestinal disease. Similar levels of NK activity were detected among the different disease groups. Within the inflammatory bowel disease patient group, however, C...

Antibody-based immunotherapy represents a promising strategy to eliminate chemorefractory leukemic cells in acute myeloid leukemia (AML). In this study, we evaluated a novel Fc-engineered antibody against CD157 (MEN1112) for its suitability as immunotherapy in AML. CD157 was expressed in 97% of primary AML patient samples. A significant, albeit lower expression level of CD157 was observed withi...

Impairment of natural killer (NK) cell activity is an important mechanism of tumor immunoevasion. We have previously shown that expression of granulin-epithelin precursor (GEP) in hepatocellular carcinoma (HCC) cells rendered the cells resistant to NK cell immunosurveillance. Here, we examined whether targeting GEP could rescue NK activity in HCC patients. The current study demonstrated that qu...