Defective antigen-presenting cell function of MDSCs from late stage tumor-bearing mice can be recovered by ATRA treatment. (100.3)

Abstract

Abstract Myeloid-derived suppressor cells (MDSCs), which accumulate during tumor progression, have recently been shown to function as the main suppressor cells. In our previous study, we showed that poorly immunogenic MDSCs could function as immunogenic antigen presenting cells (APCs) with the help of activated natural killer T (NKT) cells. However, depending on the tumor stage, we found that MDSCs had variable capacity as APCs. NKT ligand-loaded MDSCs from late stage tumor-bearing mice (late MDSCs) were less immunogenic as APCs compared to those from early stage tumor-bearing mice. As tumor growth progresses, surface molecule expression required for APC function on MDSCs was largely down-regulated. NKT ligand-loaded late MDSCs were also poorly differentiated and induced decreased NKT activation and antigen-specific cytotoxic T lymphocyte (CTL) response. However, these functional defects were recovered by the treatment of all-trans retinoic acid (ATRA). NKT ligand-loaded, ATRA-treated late MDSCs were able to be transformed into immunogenic APCs to induce incremental immune responses. These effects were accompanied by the recovered activation and differentiation of late MDSCs. Collectively, we concluded that although the functional defect of MDSCs as APCs was found with tumor progression, it can be recovered by treatment with ATRA. Therefore, these findings suggest that late MDSCs can function as effective APCs.