Chaetocin enhances dendritic cell function via the induction of heat shock protein and cancer testis antigens in myeloma cells

// Manh-Cuong Vo 1, * , Thanh-Nhan Nguyen-Pham 1, 2, * , Hyun-Ju Lee 1 , Sung-Hoon Jung 1, 2 , Nu-Ri Choi 1 , My-Dung Hoang 1 , Hyeoung-Joon Kim 2 and Je-Jung Lee 1, 2 1 Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea 2 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea * These authors have contributed equally to this work Correspondence to: Je-Jung Lee, email: drjejung@chonnam.ac.kr Keywords: chaetocin, dendritic cells, multiple myeloma Received: April 25, 2016     Accepted: March 24, 2017     Published: April 29, 2017 ABSTRACT Dendritic cells (DC)-based vaccines are considered useful in cancer immuno-therapy, and the interactions of DC and dying tumor cells are important and promising for cancer immunotherapy. We investigated whether chaetocin could be used to induce death of myeloma cells, for loading onto DCs can affect DCs function. In this study, we show that the dying myeloma cells treated with chaetocin resulted in the induction of heat shock protein (HSP) 90, which was inhibited by antioxidant N-acetyl cysteine, and showed an increase in the expression of MAGE-A3 and MAGE-C1/CT7. DCs loaded with chaetocin-treated dying myeloma cells produced low levels of IL-10 and enhanced the cross presentation of DCs. Additionally, these DCs most potently inhibited regulatory T cells, induced Th1 polarization and activated myeloma-specific cytotoxic T lymphocytes compared with DCs loaded with UVB-irradiated dying myeloma cells. These results suggest that the pretreatment of myeloma cells with chaetocin can enhance DC function through the up-regulation of HSP90 and cancer testis antigens in dying myeloma cells and can potently induce the Th1 polarization of DCs and myeloma-specific cytotoxic T lymphocytes.