Invariant NKT (iNKT) cells constitute a distinct lymphocyte subset, and upon activation, iNKT cells modulate the function of a wide variety of other immune cells including anti-tumor effector cells in both a direct and indirect manner. Decreased numbers and a reduced function of iNKT cells have been observed in patients with various malignant diseases, thus correlating with a poor clinical outcome. Therefore, therapeutic intervention strategies aimed at the recovery of functional iNKT cells would be an appropriate rationale for the treatment of cancer. Early clinical trials of iNKT cell-based immunotherapy demonstrated that the infusion of ligand-pulsed antigen presenting cells and/or in vitro activated iNKT cells was safe and well tolerated. This review summarizes the results of a series of clinical trials for lung cancer and head and neck cancer patients in Chiba University Hospital, Japan, and discusses iNKT cell-induced immune responses particularly those in the tumor microenvironment.
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