PMID- 32486094 OWN - NLM STAT- MEDLINE DCOM- 20210301 LR - 20210301 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 12 IP - 6 DP - 2020 May 29 TI - Annona muricata L.-Derived Polysaccharides as a Potential Adjuvant to a Dendritic Cell-Based Vaccine in a Thymoma-Bearing Model. LID - 10.3390/nu12061602 [doi] LID - 1602 AB - Dendritic cells (DCs) are powerful antigen-presenting cells that are often used to evaluate adjuvants, particularly for adjuvant selection for various vaccines. Here, polysaccharides (named ALP) isolated from leaves of Annona muricata L., which are used in traditional medicine such as for bacterial infections and inflammatory diseases, were evaluated as an adjuvant candidate that can induce anti-tumor activity. We first confirmed the phenotypic (surface molecules, cytokines, antigen uptake, and antigen-presenting ability) and functional alterations (T cell proliferation/activation) of DCs in vitro. We also confirmed the adjuvant effect by evaluating anti-tumor activity and immunity using an ALP-treated DC-immunized mouse model. ALP functionally induced DC maturation by up-regulating the secretion of Th1-polarizing pro-inflammatory cytokines, the expression of surface molecules, and antigen-presenting ability. ALP triggered DC maturation, which is dependent on the activation of the MAPK and NF-kappaB signaling pathways. ALP-activated DCs showed an ample capacity to differentiate naive T cells to Th1 and activated CD8(+) T cells effectively. The systemic administration of DCs that pulse ALP and ovalbumin peptides strongly increased cytotoxic T lymphocyte (CTL) activity (by 9.5% compared to that in the control vaccine groups), the generation of CD107a-producing multifunctional T cells, and Th1-mediated humoral immunity, and caused a significant reduction (increased protection by 29% over that in control vaccine groups) in tumor growth. ALP, which triggers the Th1 and CTL response, provides a basis for a new adjuvant for various vaccines. FAU - Kim, Woo Sik AU - Kim WS AD - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. FAU - Han, Jeong Moo AU - Han JM AD - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. AD - Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 136-701, Korea. FAU - Song, Ha-Yeon AU - Song HY AD - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. AD - Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 136-701, Korea. FAU - Byun, Eui-Hong AU - Byun EH AD - Department of Food Science and Technology, Kongju National University, Yesan 340-800, Korea. FAU - Lim, Seung-Taik AU - Lim ST AD - Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 136-701, Korea. FAU - Byun, Eui-Baek AU - Byun EB AD - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea. LA - eng GR - NRF-2019R1C1C1002484/This work was supported by the Basic science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning/ PT - Journal Article DEP - 20200529 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Adjuvants, Immunologic) RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Polysaccharides) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - *Adjuvants, Immunologic MH - Animals MH - Annonaceae/*chemistry MH - Antigen Presentation MH - *Cancer Vaccines MH - Cytokines/metabolism MH - Dendritic Cells/*immunology MH - Female MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - *Polysaccharides/immunology/isolation & purification/pharmacology MH - Signal Transduction/drug effects/immunology MH - T-Lymphocytes/immunology MH - Thymoma/*immunology/therapy MH - Thymus Neoplasms/*immunology/therapy PMC - PMC7352220 OTO - NOTNLM OT - Annona muricata L. OT - Th1 OT - cytotoxic T lymphocyte OT - dendritic cells OT - multifunctional T cells OT - polysaccharide OT - vaccine adjuvant COIS- The authors declare no conflict of interest. EDAT- 2020/06/04 06:00 MHDA- 2021/03/02 06:00 PMCR- 2020/06/01 CRDT- 2020/06/04 06:00 PHST- 2020/04/28 00:00 [received] PHST- 2020/05/23 00:00 [revised] PHST- 2020/05/27 00:00 [accepted] PHST- 2020/06/04 06:00 [entrez] PHST- 2020/06/04 06:00 [pubmed] PHST- 2021/03/02 06:00 [medline] PHST- 2020/06/01 00:00 [pmc-release] AID - nu12061602 [pii] AID - nutrients-12-01602 [pii] AID - 10.3390/nu12061602 [doi] PST - epublish SO - Nutrients. 2020 May 29;12(6):1602. doi: 10.3390/nu12061602.