PMID- 33921475 OWN - NLM STAT- MEDLINE DCOM- 20210512 LR - 20210512 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 8 DP - 2021 Apr 12 TI - Thapsigargin-Stimulated LAD2 Human Mast Cell Line Is a Potent Cellular Adjuvant for the Maturation of Monocyte-Derived Dendritic Cells for Adoptive Cellular Immunotherapy. LID - 10.3390/ijms22083978 [doi] LID - 3978 AB - The preparation of dendritic cells (DCs) for adoptive cellular immunotherapy (ACI) requires the maturation of ex vivo-produced immature(i) DCs. This maturation ensures that the antigen presentation triggers an immune response towards the antigen-expressing cells. Although there is a large number of maturation agents capable of inducing strong DC maturation, there is still only a very limited number of these agents approved for use in the production of DCs for ACI. In seeking novel DC maturation agents, we used differentially activated human mast cell (MC) line LAD2 as a cellular adjuvant to elicit or modulate the maturation of ex vivo-produced monocyte-derived iDCs. We found that co-culture of iDCs with differentially activated LAD2 MCs in serum-containing media significantly modulated polyinosinic:polycytidylic acid (poly I:C)-elicited DC maturation as determined through the surface expression of the maturation markers CD80, CD83, CD86, and human leukocyte antigen(HLA)-DR. Once iDCs were generated in serum-free conditions, they became refractory to the maturation with poly I:C, and the LAD2 MC modulatory potential was minimized. However, the maturation-refractory phenotype of the serum-free generated iDCs was largely overcome by co-culture with thapsigargin-stimulated LAD2 MCs. Our data suggest that differentially stimulated mast cells could be novel and highly potent cellular adjuvants for the maturation of DCs for ACI. FAU - Taborska, Pavla AU - Taborska P AUID- ORCID: 0000-0001-5935-5656 AD - Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, 15006 Prague, Czech Republic. FAU - Stakheev, Dmitry AU - Stakheev D AD - Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, 15006 Prague, Czech Republic. FAU - Bartunkova, Jirina AU - Bartunkova J AD - Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, 15006 Prague, Czech Republic. FAU - Smrz, Daniel AU - Smrz D AUID- ORCID: 0000-0003-0143-8744 AD - Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, 15006 Prague, Czech Republic. LA - eng GR - PRIMUS/MED/12/Univerzita Karlova v Praze/ GR - AZV 16-28135A/Ministerstvo Zdravotnictvi Ceske Republiky/ PT - Journal Article DEP - 20210412 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Adjuvants, Immunologic) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Antigen Presentation/drug effects/immunology MH - Cell Culture Techniques/*methods MH - Cell Differentiation/drug effects MH - Coculture Techniques MH - Dendritic Cells/cytology/*drug effects/immunology MH - Female MH - Humans MH - *Immunotherapy, Adoptive MH - Mast Cells/cytology/*drug effects/immunology MH - Monocytes/cytology/drug effects/immunology MH - Thapsigargin/pharmacology PMC - PMC8069665 OTO - NOTNLM OT - LAD2 human mast cells OT - adoptive cellular immunotherapy OT - dendritic cells OT - maturation COIS- J.B. is a part-time employee and a minority shareholder of Sotio, a.s., a biotech company developing cell-based immunotherapy. P.T., D.S. (Dmitry Stakheev), and D.S. (Daniel Smrz) declare no conflicts of interest. EDAT- 2021/05/01 06:00 MHDA- 2021/05/13 06:00 PMCR- 2021/04/12 CRDT- 2021/04/30 01:19 PHST- 2021/03/02 00:00 [received] PHST- 2021/03/23 00:00 [revised] PHST- 2021/04/07 00:00 [accepted] PHST- 2021/04/30 01:19 [entrez] PHST- 2021/05/01 06:00 [pubmed] PHST- 2021/05/13 06:00 [medline] PHST- 2021/04/12 00:00 [pmc-release] AID - ijms22083978 [pii] AID - ijms-22-03978 [pii] AID - 10.3390/ijms22083978 [doi] PST - epublish SO - Int J Mol Sci. 2021 Apr 12;22(8):3978. doi: 10.3390/ijms22083978.