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Effective induction of melanoma‐antigen‐specific CD 8 + T cells via V γ 9 γδ T cell expansion by CD 56 high+ Interferon‐ α ‐induced dendritic cells
Author(s) -
Nieda Mie,
Terunuma Hiroshi,
Eiraku Yuuta,
Deng Xuewen,
Nicol Andrew J.
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12581
Subject(s) - cd14 , cd86 , antigen , antigen presenting cell , immune system , cd40 , immunology , granulocyte macrophage colony stimulating factor , cytotoxic t cell , biology , cytokine , chemistry , t cell , in vitro , microbiology and biotechnology , biochemistry
Dendritic cells (DCs) can be differentiated from CD14 + monocytes in the presence of interferon‐ α (IFN α ) 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‐ α (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 + V γ 9 γδ T cells highly producing IFN γ 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 + V γ 9 γδ T 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.