자연살해세포 특이 수용체의 상승효과를 통한 전혈 내 자연살해세포 활성 평가

Abstract

Natural killer (NK) cells are cytotoxic innate lymphocytes endowed with an ability to mediate immune-surveillance of cancer cells and virus-infected cells. The measurement of NK cell activity (NKA) can be utilized as a prognostic and therapeutic marker in diverse diseases, considering their activity is associated with disease stage and severity. Current NKA assays have shortcoming including cautious labeling and handling of target cells and/or NK cells and require a rapid isolation of peripheral blood mononuclear cells (PBMCs) that often require large amounts of blood. In this study, an ELISA-based whole blood (WB) NKA assay was developed including engineered target cells (P815-ULBP1+CD48) that induces NK-specific synergistic stimulation via NKG2D and 2B4. NKA in WB collected from healthy donors (HDs) and patients with multiple myeloma (MM) was evaluated to confirm the clinical usefulness of the WB NKA assay. NKA was significantly lower in MM than in HD after stimulation with P815-ULBP1+CD48 and had a good correlation with the commonly used flow cytometry-based PBMC NKA assay. The use of defined P815-ULBP1+CD48 cells has facilitated mechanistic studies involved in assessing the levels of NKG2D and 2B4 in NK cells and led to the identification of TGF-β1 as an important mediator of impaired NKA in MM. In conclusion, the WB NKA assay facilitates the rapid and reliable measurement of NKA and has promising potential for further development as a clinical and research tool.