Mouse CD8(+)NKT-like cells exert dual cytotoxicity against mouse tumor cells and myeloid-derived suppressor cells

Our previous work has demonstrated the high efficiency of CD8(+) natural killer T (NKT)-like cells in killing antigen-bearing dendritic cells. To evaluate their role in the tumor microenvironment, we performed in vitro and in vivo antitumor experiments to investigate whether CD8(+)NKT-like cells could kill Yac-1 and B16 cells like NK cells and kill EL4-OVA8 cells in an antigen-specific manner like cytotoxic T lymphocytes (CTLs). Unlike NK1.1(−)CTLs, CD8(+)NKT-like cells also exhibit the capability to kill myeloid-derived suppressor cells (MDSCs) in an antigen-specific manner, indicative of their potential role in clearing tumor antigen-bearing MDSCs to improve the antitumor microenvironment. In vitro blocking experiments showed that granzyme B inhibitor efficiently suppressed the cytotoxicity of CD8(+)NKT-like cells against tumor cells and MDSCs, while Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibition failed to produce similar effects. Transcriptomic and phenotypic analyses of CD8(+)NKT-like cells, NK cells, and NK1.1(−)CTLs indicated that CD8(+)NKT-like cells expressed both T-cell activation markers and NK cell markers, thus bearing features of both the activated T cells and NK cells. Taken together, CD8(+)NKT-like cells could exert NK- and CTL-like antitumor effects through the elimination of both tumor cells and MDSCs in a granzyme B-dependent manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02363-3) contains supplementary material, which is available to authorized users.