Jun Ding1, Tongbao Feng2, Yongling Ning2, Wenjing Li2, Qiyong Wu3, Keqing Qian2, Yong Wang1, Chunjian Qi4. 1. Oncology Institute, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou 213003, China; Deparment of Cardiothoracic Surgery, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou 213003, China. 2. Oncology Institute, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou 213003, China. 3. Deparment of Cardiothoracic Surgery, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou 213003, China. 4. Oncology Institute, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou 213003, China. Electronic address: qichunjian@gmail.com.
Abstract
PURPOSE: To investigate the effects of β-(1,3/1,6)-d-glucan on dendritic cells (DCs) maturation, cytotoxic T lymphocyte responses and the molecular mechanisms of its transition. METHODS AND RESULTS: Human monocyte-derived DCs were matured using yeast-derived particulate β-glucan (WGP) or a mix of TNF-α, IL-1β and IL-6 ("Conv mix"). Multicolor flow cytometry was used to study the DCs phenotype and cytotoxic T-lymphocyte priming and differentiation. ELISA and RT-PCR assays were used to evaluate cytokine production. Western blot was used to investigate the signal pathways. WGP-matured DCs functions were compared with those of Conv mix-matured DCs. WGP-matured DCs expressed higher levels of CD11c, CD86, CD40 and HLA-DR; produced higher levels of pro-inflammatory cytokines; and elicited more CTL priming and differentiation than Conv mix-matured DCs. The PI3K/AKT signaling pathway was involved in WGP-induced dendritic cell maturation. Furthermore, WGP-matured DCs significantly increased tumor-specific CTL responses. CONCLUSION: Excellent ability of yeast-derived particulate β-glucan to induce DCs maturation and tumor-specific CTL responses explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DCs generated for therapy.
PURPOSE: To investigate the effects of β-(1,3/1,6)-d-glucan on dendritic cells (DCs) maturation, cytotoxic T lymphocyte responses and the molecular mechanisms of its transition. METHODS AND RESULTS:Human monocyte-derived DCs were matured using yeast-derived particulate β-glucan (WGP) or a mix of TNF-α, IL-1β and IL-6 ("Conv mix"). Multicolor flow cytometry was used to study the DCs phenotype and cytotoxic T-lymphocyte priming and differentiation. ELISA and RT-PCR assays were used to evaluate cytokine production. Western blot was used to investigate the signal pathways. WGP-matured DCs functions were compared with those of Conv mix-matured DCs. WGP-matured DCs expressed higher levels of CD11c, CD86, CD40 and HLA-DR; produced higher levels of pro-inflammatory cytokines; and elicited more CTL priming and differentiation than Conv mix-matured DCs. The PI3K/AKT signaling pathway was involved in WGP-induced dendritic cell maturation. Furthermore, WGP-matured DCs significantly increased tumor-specific CTL responses. CONCLUSION: Excellent ability of yeast-derived particulate β-glucan to induce DCs maturation and tumor-specific CTL responses explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DCs generated for therapy.
Authors: Phyu M Thwe; Daniel I Fritz; Julia P Snyder; Portia R Smith; Kylie D Curtis; Alexandra O'Donnell; Nicholas A Galasso; Leslie A Sepaniac; Benjamin J Adamik; Laura R Hoyt; Princess D Rodriguez; Tyler C Hogan; Andrea F Schmidt; Matthew E Poynter; Eyal Amiel Journal: J Leukoc Biol Date: 2019-09-11 Impact factor: 4.962