Initial in vitro studies of the memory-like NK cells (generated through preactivation with IL-12, IL-15, and IL-18 for 12-16hours followed by 1 week of rest with low-dose IL-15 to allow for differentiation) revealed that memory-like NK cells have very distinct phenotypes on mass cytometry analysis, though KIR expression remained unaltered.
Phase I clinical trials demonstrated that the anti-inhibitory KIR mAb is safe [60], and phase II clinical trials with lirilumab are ongoing.
Their antileukemic effect is mostly related to the presence of "alloreactive" NK cells, though an important role is also played by certain activating KIR (primarily, but not only, KIR2DS1) upon interaction with their HLA class I ligand (C2 alleles).
Falco et al., "Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity," Blood, vol.
Gonzelez, "The extensive polymorphism of KIR genes," Immunology, vol.
Mezger et al., "KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with all," Blood, vol.
In conclusion, we demonstrated that Juzen-taiho-to upregulated the expression of
KIRs. These effects contribute to the augmentation of NK cytolytic activity, and might explain, in part, its antitumor effects which were observed in vivo (Hamada et al., 1988; Ohnishi et al., 1996; Ohnishi et al., 1998; Horie et al., 1992).
This result supports further that KIR and HLA combinations can influence the onset age of HCC.
To further refine programs for those at highest risk of unresectable HCC, we explored the association between KIR locus, HLA ligand, and HLA-KIR combination with the TNM stages of HCC at diagnosis.
To our knowledge, this is the first report on the association between KIR and HLA genetic background and the onset age of HCC.
Romagne, "NK cell MHC class I specific receptors (KIR): from biology to clinical intervention," Current Opinion in Immunology, vol.
Sun et al., "KIR and HLA loci are associated with hepatocellular carcinoma development in patients with hepatitis B virus infection: a case-control study," PLoS ONE, vol.