PMID- 25363560 OWN - NLM STAT- MEDLINE DCOM- 20151117 LR - 20201222 IS - 1600-0625 (Electronic) IS - 0906-6705 (Linking) VI - 24 IP - 1 DP - 2015 Jan TI - Effective induction of melanoma-antigen-specific CD8+ T cells via Vgamma9gammadeltaT cell expansion by CD56(high+) Interferon-alpha-induced dendritic cells. PG - 35-41 LID - 10.1111/exd.12581 [doi] AB - Dendritic cells (DCs) can be differentiated from CD14+ monocytes in the presence of interferon-alpha (IFNalpha) and granulocyte/macrophage-colony stimulating factor (GM-CSF) in vitro and are known as IFN-DCs. Circulating blood CD56+ cells expressing high levels of CD14, HLA-DR and CD86 have been shown to spontaneously differentiate into DC-like cells in vitro after their isolation from blood. We show here that IFN-DCs expressing high levels of CD56 (hereafter, CD56(high+) IFN-DCs) can be differentiated in vitro from monocytes obtained as adherent cells from healthy donors and patients with metastatic melanoma. These cells expressed high levels of CD14, HLA-DR and CD86 and possessed many pseudopodia. These CD56(high+) IFN-DCs may be an in vitro counterpart of the circulating CD56+ CD14+ CD86+ HLA-DR+ cells in blood. Conventional mature DCs differentiated from monocytes as adherent cells in the presence of GM-CSF, IL-4 and TNF-alpha (hereafter, mIL-4DCs) did not express CD56 or CD14. In contrast to mIL-4DCs, the CD56(high+) IFN-DCs exhibited a stronger capacity to stimulate autologous CD56+ Vgamma9gammadeltaT cells highly producing IFNgamma in the presence of zoledronate and IL-2. The CD56(high+) IFN-DCs possessing HLA-A*0201 effectively induced Mart-1-modified melanoma peptide (A27L)-specific CD8+ T cells through preferential expansion of CD56+ Vgamma9gammadeltaT cells in the presence of A27L, zoledronate and IL-2. Vaccination with CD56(high+) IFN-DCs copulsed with tumor antigens and zoledronate may orchestrate the induction of various CD56+ immune cells possessing high effector functions, resulting in strong immunological responses against tumor cells. This study may be relevant to the design of future clinical trials of CD56(high+) IFN-DCs-based immunotherapies for patients with melanoma. CI - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Nieda, Mie AU - Nieda M AD - Biotherapy Institute of Japan, Koutou-ku, Tokyo, Japan. FAU - Terunuma, Hiroshi AU - Terunuma H FAU - Eiraku, Yuuta AU - Eiraku Y FAU - Deng, Xuewen AU - Deng X FAU - Nicol, Andrew J AU - Nicol AJ LA - eng PT - Journal Article DEP - 20141208 PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (CD56 Antigen) RN - 0 (Diphosphonates) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (Imidazoles) RN - 0 (Interferon-alpha) RN - 0 (Interleukin-2) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Peptides) RN - 0 (Receptors, Antigen, T-Cell, gamma-delta) RN - 0 (T-cell receptor Vgamma9, human) RN - 6XC1PAD3KF (Zoledronic Acid) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - CD56 Antigen/*metabolism MH - CD8-Positive T-Lymphocytes/*cytology MH - Dendritic Cells/*metabolism MH - Diphosphonates/chemistry MH - Flow Cytometry MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - HLA-A2 Antigen/metabolism MH - Humans MH - Imidazoles/chemistry MH - Immunotherapy MH - Interferon-alpha/*metabolism MH - Interleukin-2/metabolism MH - Leukocytes, Mononuclear/cytology MH - Lipopolysaccharide Receptors/metabolism MH - Lymphocytes/cytology MH - Melanoma/immunology/*metabolism/therapy MH - Monocytes/cytology MH - Peptides/metabolism MH - Phenotype MH - Receptors, Antigen, T-Cell, gamma-delta/*immunology MH - Skin Neoplasms/immunology/metabolism/therapy MH - Zoledronic Acid OTO - NOTNLM OT - IFN alpha OT - Vgamma9gammadeltaT OT - immunotherapy OT - melanoma-antigen-specific CD8+ T OT - zoledronate EDAT- 2014/11/05 06:00 MHDA- 2015/11/18 06:00 CRDT- 2014/11/04 06:00 PHST- 2014/10/28 00:00 [accepted] PHST- 2014/11/04 06:00 [entrez] PHST- 2014/11/05 06:00 [pubmed] PHST- 2015/11/18 06:00 [medline] AID - 10.1111/exd.12581 [doi] PST - ppublish SO - Exp Dermatol. 2015 Jan;24(1):35-41. doi: 10.1111/exd.12581. Epub 2014 Dec 8.