Preferential Expansion of Th1 type-CD56+Vγ9γδT Cells by CD56high+IFNa-induced Dendritic Cells Derived from Cancer Patients in vitro and in vivo

Abstract

The CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells which spontaneously differentiate into enlarged DC (dendritic cell)-like cells. We show here that interferon-α (IFN-α)-induced DC-like cells expressing high levels of CD56 and CD14 (hereafter, CD56high+IFNDCs) can be differentiated from monocytes obtained as adherent cells from patients with various cancers, in the presence of IFN-α and granulocyte-macrophage colony stimulating factor (GM-CSF) in vitro. These cells expressed high levels of CD14, CD86, and HLA-DR and may be an in vitro counterpart of the circulating CD14+CD86+HLA-DR+ cells in blood. In contrast to conventional mature IL-4DCs which are differentiated from monocytes as adherent cells in the presence of GM-CSF, IL-4, and TNF-α (hereafter, mIL-4DCs), the CD56 high+ IFN-DCs exhibited a stronger capacity in stimulating autologous CD56+Vγ9γδT cells expressing high levels of CD16 which produced high amounts of IFNγ and TNF-α, in comparison with the mIL-4DCs. Intravenous administration of a large number of Vγ9γδT cells activated by CD56high+IFN-DCs pulsed with zoledronate (hereafter, CD56 high+ IFN-DC-activated Vγ9γδT cells) to patients with a non-small cell lung cancer resulted in the increase of PB Vγ9γδT cells among which CD56+Vγ9γδT cells and CD16+Vγ9γδT cells predominantly increased in vivo. Among γδT cell-based immunotherapy, vaccination with CD56high+IFN-DCactivated Vγ9γδT cells may lead to improved clinical outcomes of patients with cancer.