Xuewen Deng

Biotherapy Institute of Japan

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Hiroshi Terunuma

Biotherapy Institute of Japan

Mie Nieda

University of Queensland

Naoki Yamamoto

National Center for Global Health and Medicine

Masahiko Ito

Hamamatsu University School of Medicine

Baskar Subramani

Asia School of Business

Ray Handema

Tropical Diseases Research Centre

Atsushi Terunuma

Tsukuba Memorial Hospital

Hirotake Kasai

University of Yamanashi

Atsushi Toki

Hamamatsu University School of Medicine

Kazuo Watanabe

National Cancer Center Hospital East

Cooperative Institutions

Biotherapy Institute of Japan

University of Yamanashi

Southern Tohoku General Hospital

Institute for Stem Cell Biology and Regenerative Medicine

University Teaching Hospital

University of Yamanashi Hospital

National Institute of Infectious Diseases

Tokyo Medical and Dental University

Kyoto University

MRC Centre for Regenerative Medicine

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Higher prevalence and viral load of TT virus in saliva than in the corresponding serum: Another possible transmission route and replication site of TT virus

Journal of Medical Virology (2000)

Xuewen Deng Hiroshi Terunuma Ray Handema Minoru Sakamoto Takatoshi Kitamura

Although TT virus (TTV) is transmissible by blood or blood products, many patients with no history of transfusion of blood and blood products have been shown to be infected, suggesting other possible routes of transmission. To investigate the transmission routes and replication sites of TTV, 85 paired saliva and serum samples were studied by semi-nested polymerase chain reaction. The prevalence of TTV DNA was 38% (32/85 samples) and 21% (18/85) in saliva and serum, respectively. Fifteen patients had TTV DNA both in saliva and serum. Six out of fifteen patients had significantly higher viral titers in saliva than in serum, but none had higher titer in serum than in saliva. When the 222 base-pair nucleotide sequences of PCR products amplified from the samples were analyzed, 12 patients had the same genotype/subtype in saliva and serum and exhibited high homology (96-100%). The other 3 had different genotypes/subtypes in saliva and serum, and the homology was 61.9-87.2%. Mixed infection was observed both in saliva and serum. Further studies are required to determine if a subgroup of TTV has tropism to saliva. The high prevalence and viral load of TTV in saliva suggest that salivary fluid may be a possible route of transmission of TTV and that TTV might replicate not only in liver tissue but also in other tissues such as oropharyngeal tissues and/or salivary glands.

Replication

10.1002/1096-9071(200012)62:4<531::aid-jmv20>3.0.co;2-c

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Citations (76)

Mild Hyperthermia Modulates the Relative Frequency of Lymphocyte Cell Subpopulations: an Increase in a Cytolytic NK Cell Subset and a Decrease in a Regulatory T Cell Subset

Thermal Medicine(Japanese Journal of Hyperthermic Oncology) (2007)

Hiroshi Terunuma AYANO WADA Xuewen Deng Yoshihide Yasuma Tetsuro Onishi

Although mild hyperthermia (MHT) cannot directly kill tumor cells, an augmented immunological effect resulting from MHT has been reported to induce injury of malignant tumors. In this study, the impact of regional MHT on lymphocyte subpopulations was investigated. Of particular interest was the effect of MHT on natural killer (NK) cells and T cells, which are important in the innate and adaptive immune systems. Regional MHT treatment was performed using an 8-MHz capacitive heating device, the Thermotron RF8 (Yamamoto Vinita Co., Ltd., Osaka, Japan). An average continuous radio-frequency irradiation of approximately 900 W was applied between two 30-cm electrodes placed on opposite sides of a volunteer's upper abdominal region for 30 min. In healthy volunteers exposed to this thermal treatment, NK cell activity and the percentage of NK cells and cytolytic NK cells (CD3-CD56dim cells) in lymphocyte populations increased significantly at 1 and 7 days after regional MHT treatment compared with pre-treatment numbers. The number of cytolytic NK cells also increased significantly at 1 day after treatment. The percentage of T cells and CD4+ T cells decreased significantly from 1 to 7 days following the heating procedure. However, no significant changes in the percentage and the number of CD8+ T cells was observed. Interestingly, the percentage and the number of CD4+CD25+ T lymphocytes which are recognized as regulatory T lymphocytes (Treg) decreased significantly during the 7 day post-treatment period. These results suggest that regional MHT may activate both, the innate and adaptive immune systems, through activation of NK cells and through a decrease in the number of regulatory T cells.

10.3191/thermalmedicine.23.41

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Citations (14)

Combining Hyperthermia and Immunotherapy: NK Therapy and Hyperthermia

Springer eBooks (2016)

Hiroshi Terunuma Noriyuki Nishino Tsuyoshi Abe Akiko Yoshimura Atsushi Toki

Cancer Immunotherapy

Ex vivo

Lymphokine-activated killer cell

10.1007/978-981-10-0719-4_29

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Natural killer activity of peripheral-blood mononuclear cells in breast cancer patients

Biomedicine & Pharmacotherapy (2009)

Md. Zahidunnabi Dewan Masahiro Takada Hiroshi Terunuma Xuewen Deng Sunjida Ahmed

10.1016/j.biopha.2009.02.003

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Citations (47)

Synergistic cytotoxicity of ex vivo expanded natural killer cells in combination with monoclonal antibody drugs against cancer cells

International Immunopharmacology (2012)

Xuewen Deng Hiroshi Terunuma Mie Nieda Weihua Xiao Andrew J. Nicol

NK-92

Lymphokine-activated killer cell

Cancer Immunotherapy

Janus kinase 3

10.1016/j.intimp.2012.09.014

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Citations (40)

Effective induction of melanoma‐antigen‐specific CD8⁺ T cells via Vγ9γδT cell expansion by CD56^high+ Interferon‐α‐induced dendritic cells

Experimental Dermatology (2014)

Mie Nieda Hiroshi Terunuma Yuuta Eiraku Xuewen Deng Andrew J. Nicol

Abstract 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.

CD86

10.1111/exd.12581

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Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients

Biomedical Reports (2014)

Baskar Subramani Chithra Ramanathan Pullai KOHILA KRISHNAN SHEELA DEVI SUGADAN Xuewen Deng

Immune cell‑based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced‑toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the ex vivo activation and expansion of NK and T cells was performed in good manufacturing practice‑certified clean rooms for ~12‑15 days. Immunophenotypic analysis of the peripheral blood mononuclear cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and the patients were followed up. On average, 4.8x107 initial PBMCs and 2.7x109 total expanded cells were obtained. The intravenous infusions of the expanded cells were not accompanied by adverse reactions. Improved prognosis, reflected by a considerable decrease in the cancer markers, accompanied by an improved quality of life in the patients were observed. In conclusion, potential strategies are currently under development for the large‑scale production of effectors cells; therefore, autologous immune enhancement therapy (AIET) may be considered as a viable approach to cancer treatment.

Ex vivo

Lymphokine-activated killer cell

10.3892/br.2014.264

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Citations (8)

Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging

Biomedicines (2021)

Xuewen Deng Hiroshi Terunuma Mie Nieda

Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections. However, functional alterations of human NK cells are associated with lifestyles and aging. Personal lifestyles, such as cigarette smoking, alcohol consumption, stress, obesity, and aging are correlated with NK cell dysfunction, whereas adequate sleep, moderate exercise, forest bathing, and listening to music are associated with functional healthy NK cells. Therefore, adherence to a healthy lifestyle is essential and will be favorable for immunosurveillance of cancer and viral infections with healthy NK cells.

Immunosurveillance

NK-92

10.3390/biomedicines9050557

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Citations (12)

Potential Role of NK Cells in the Induction of Immune Responses: Implications for NK Cell–Based Immunotherapy for Cancers and Viral Infections

International Reviews of Immunology (2008)

Hiroshi Terunuma Xuewen Deng Zahidunnabi Dewan Shigeyoshi Fujimoto Naoki Yamamoto

Natural killer (NK) cells recognize tumor cells and virus-infected cells and attack without being sensitized to antigens. The development of the antitumor/antivirus activities of NK cells is controlled by multiple mechanisms such as direct cytotoxic activity against target cells, antibody-dependent cell-mediated cytotoxicity, secretion of Th1-type cytokines, and interactions with dendritic cells. The development of these activities plays a significant role in both innate and adaptive immunities. Considering the recent progress made in elucidating the molecular and cellular biology of NK cells, we summarize the current situation and discuss future possibilities with regard to NK cell–based adoptive immunotherapy.

Lymphokine-activated killer cell

NK-92

Cancer Immunotherapy

10.1080/08830180801911743

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Citations (89)

Adoptive NK cell therapy: a potential revolutionary approach in longevity therapeutics

Immunity & Ageing (2024)

Xuewen Deng Hiroshi Terunuma

Abstract The aging process intricately involves immune system dynamics, with a crucial role in managing senescent cells (SNCs) and their senescence-associated secretory phenotypes (SASPs). Unfortunately, immunosenescence, a progressively dysregulated immunity with age, hampers effective SNC elimination, leading to accumulation, coupled with the release of SASPs, which, in turn, inhibits immunity and heightened susceptibility to aging-associated diseases (AADs). Natural killer (NK) cells, integral to the innate immune system, play a pivotal role in addressing SNCs swiftly. These cells also coordinate with other components of both innate and adaptive immunity to surveil and eliminate these cells. Accordingly, preserving NK cell function during aging is crucial for evading AADs and promoting healthy aging. Alternatively, NK-cell-based therapies present promising avenues for addressing the challenges associated with aging. Notable, recent studies in adoptive NK cell therapy have shown promise in rejuvenating immunosenescence, eliminating SNCs, and alleviating SASPs. This progress provides the proof-concept of adoptive NK cell therapy for senotherapy and holds promise as an emerging revolution in longevity therapeutics.

Immunosenescence

Senescence

Cell therapy

Adoptive Cell Transfer

10.1186/s12979-024-00451-2

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Citations (3)