PMID- 29754770 OWN - NLM STAT- MEDLINE DCOM- 20190913 LR - 20190913 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 20 IP - 6 DP - 2018 Jun TI - Skewing effect of sulprostone on dendritic cell maturation compared with dinoprostone. PG - 851-860 LID - S1465-3249(18)30485-7 [pii] LID - 10.1016/j.jcyt.2018.04.002 [doi] AB - BACKGROUND: Dendritic cells (DCs) are the most efficient antigen-presenting cells and act at the center of the immune system owing to their ability to control both immune tolerance and immunity. In cancer immunotherapy, DCs play a key role in the regulation of the immune response against tumors and can be generated ex vivo with different cytokine cocktails. METHODS: We evaluated the feasibility of dinoprostone (PGE(2)) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine. We characterized the phenotype and the function of DCs matured in the presence of sulprostone as a potential substitute of dinoprostone in the pro-inflammatory maturation cocktail consisting of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and IL-6. RESULTS: We found that sulprostone invariably reduces the recovery, but does not significantly modify the viability and the purity of DCs. The presence of sulprostone in the maturation cocktail increases the adhesion of single cells and of clusters of DCs to the flask, making them more similar to their immature counterpart in terms of adhesion and spreading proprieties. Moreover, we observed that sulprostone impairs the expression of co-stimulatory molecules and the spontaneous as well as the directed migration capacity of DCs. DISCUSSION: These findings underscore that the synthetic analog sulprostone strongly reduces the functional quality of DCs, thus cannot replace dinoprostone in the maturation cocktail of monocyte-derived DCs. CI - Copyright (c) 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Bulgarelli, Jenny AU - Bulgarelli J AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. Electronic address: jenny.bulgarelli@irst.emr.it. FAU - Fiammenghi, Laura AU - Fiammenghi L AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Cassan, Serena AU - Cassan S AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Granato, Anna Maria AU - Granato AM AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Petrini, Massimiliano AU - Petrini M AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Pancisi, Elena AU - Pancisi E AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Soldati, Valentina AU - Soldati V AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - De Rosa, Francesco AU - De Rosa F AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Ridolfi, Laura AU - Ridolfi L AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Riccobon, Angela AU - Riccobon A AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Guidoboni, Massimo AU - Guidoboni M AD - Unit of Immunotherapy and Somatic Cell Therapy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. LA - eng PT - Comparative Study PT - Journal Article DEP - 20180510 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Cancer Vaccines) RN - 0 (Interleukin-1beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - 501Q5EQ1GM (sulprostone) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Cancer Vaccines/immunology MH - Cell Differentiation/*drug effects MH - Cells, Cultured MH - Dendritic Cells/*drug effects/physiology MH - Dinoprostone/*analogs & derivatives/*pharmacology MH - Drug Evaluation, Preclinical MH - Humans MH - Immunotherapy, Adoptive/methods MH - Interleukin-1beta/metabolism MH - Monocytes/drug effects/metabolism/physiology MH - Therapeutic Equivalency MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - cancer immunotherapy OT - dendritic cell vaccine OT - dinoprostone OT - sulprostone EDAT- 2018/05/15 06:00 MHDA- 2019/09/14 06:00 CRDT- 2018/05/15 06:00 PHST- 2017/10/16 00:00 [received] PHST- 2018/02/27 00:00 [revised] PHST- 2018/04/09 00:00 [accepted] PHST- 2018/05/15 06:00 [pubmed] PHST- 2019/09/14 06:00 [medline] PHST- 2018/05/15 06:00 [entrez] AID - S1465-3249(18)30485-7 [pii] AID - 10.1016/j.jcyt.2018.04.002 [doi] PST - ppublish SO - Cytotherapy. 2018 Jun;20(6):851-860. doi: 10.1016/j.jcyt.2018.04.002. Epub 2018 May 10.