PMID- 24482752 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20210203 LR - 20211021 IS - 2162-4011 (Print) IS - 2162-402X (Electronic) IS - 2162-4011 (Linking) VI - 2 IP - 11 DP - 2013 Nov 1 TI - CD137L-stimulated dendritic cells are more potent than conventional dendritic cells at eliciting cytotoxic T-cell responses. PG - e26859 LID - e26859 AB - Dendritic cells (DCs) are highly potent initiators of adaptive immune responses and, as such, represent promising tools for immunotherapeutic applications. Despite their potential, the current efficacy of DC-based immunotherapies is poor. CD137 ligand (CD137L) signaling has been used to derive a novel type of DCs from human peripheral blood monocytes, termed CD137L-DCs. Here, we report that CD137L-DCs induce more potent cytotoxic T-cell responses than classical DCs (cDCs). Furthermore, in exploring several DC maturation factors for their ability to enhance the potency of CD137L-DCs, we found the combination of interferon gamma (IFNgamma) and the mixed Toll-like receptor (TLR)7/8 agonist R848, to display the highest efficacy in potentiating the T-cell co-stimulatory activity of CD137L-DCs. Of particular importance, CD137L-DCs were found to be more efficient than cDCs in activating autologous T cells targeting the cytomegalovirus (CMV)-derived protein pp65. Specifically, CD137L-DC-stimulated T cells were found to secrete higher levels of IFNgamma and killed 2-3 times more HLA-matched, pp65-pulsed target cells than T cells activated by cDCs. Finally, in addition to stimulating CD8(+) T cells, CD137L-DCs efficiently activated CD4(+) T cells. Taken together, these findings demonstrate the superior potency of CD137L-stimulated DCs in activating CMV-specific, autologous T cells, and encourage the further development of CD137L-DCs for antitumor immunotherapy. FAU - Harfuddin, Zulkarnain AU - Harfuddin Z AD - Department of Physiology; National University of Singapore; Singapore ; Immunology Programme; National University of Singapore; Singapore ; NUS Graduate School for Integrative Sciences and Engineering; National University of Singapore; Singapore. FAU - Kwajah, Shaqireen AU - Kwajah S AD - Department of Physiology; National University of Singapore; Singapore. FAU - Chong Nyi Sim, Adrian AU - Chong Nyi Sim A AD - Department of Microbiology; National University of Singapore; Singapore ; Immunology Programme; National University of Singapore; Singapore. FAU - Macary, Paul Anthony AU - Macary PA AD - Department of Microbiology; National University of Singapore; Singapore ; Immunology Programme; National University of Singapore; Singapore ; NUS Graduate School for Integrative Sciences and Engineering; National University of Singapore; Singapore. FAU - Schwarz, Herbert AU - Schwarz H AD - Department of Physiology; National University of Singapore; Singapore ; Immunology Programme; National University of Singapore; Singapore ; NUS Graduate School for Integrative Sciences and Engineering; National University of Singapore; Singapore. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131111 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 PMC - PMC3897521 OTO - NOTNLM OT - CD137 OT - CMV OT - T-cell responses OT - cytomegalovirus OT - dendritic cell OT - immunotherapy EDAT- 2014/02/01 06:00 MHDA- 2014/02/01 06:01 PMCR- 2013/11/11 CRDT- 2014/02/01 06:00 PHST- 2013/07/27 00:00 [received] PHST- 2013/10/15 00:00 [revised] PHST- 2013/10/17 00:00 [accepted] PHST- 2014/02/01 06:00 [entrez] PHST- 2014/02/01 06:00 [pubmed] PHST- 2014/02/01 06:01 [medline] PHST- 2013/11/11 00:00 [pmc-release] AID - 2013ONCOIMM0208R [pii] AID - 10.4161/onci.26859 [doi] PST - ppublish SO - Oncoimmunology. 2013 Nov 1;2(11):e26859. doi: 10.4161/onci.26859. Epub 2013 Nov 11.