Effective induction of melanoma‐antigen‐specific CD8+ T cells via Vγ9γδT cell expansion by CD56high+ Interferon‐α‐induced dendritic cells |
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| Authors: | Mie Nieda Hiroshi Terunuma Yuuta Eiraku Xuewen Deng Andrew J Nicol |
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| Affiliation: | 1. Biotherapy Institute of Japan, Koutou‐ku, Tokyo, Japan;2. Tokyo Clinic, Tokyo, Japan;3. Southern Tohoku General Hospital, Fukushima, Japan;4. Centre for Immune and Targeted Therapy, Greenslopes Private Hospital, University of Queensland, Brisbane, Qld, Australia |
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| Abstract: | Dendritic cells (DCs) can be differentiated from CD14+ monocytes in the presence of interferon‐α (IFNα) 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, CD56high+ 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 CD56high+ 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 CD56high+ IFN‐DCs exhibited a stronger capacity to stimulate autologous CD56+ Vγ9γδT cells highly producing IFNγ in the presence of zoledronate and IL‐2. The CD56high+ IFN‐DCs possessing HLA‐A*0201 effectively induced Mart‐1‐modified melanoma peptide (A27L)‐specific CD8+ T cells through preferential expansion of CD56+ Vγ9γδT cells in the presence of A27L, zoledronate and IL‐2. Vaccination with CD56high+ 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 CD56high+ IFN‐DCs‐based immunotherapies for patients with melanoma. |
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| Keywords: |
IFN
α
immunotherapy melanoma‐antigen‐specific CD8+ T Vγ 9γ δ T zoledronate |
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