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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2017) | Viewed by 20587

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Prof. Dr. Ingo Schmidt-Wolf

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Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
Interests: cancer immunotherapy; NKT cells; cytokine-induced killer cells; gastrointestinal cancer

Special Issue Information

Dear Colleagues,

This Special Issue, “Natural Killer T (NKT) Cells”, will cover a selection of recent research topics and current review articles in this field. Experimental papers, up-to-date review articles and commentaries are all welcome.

Natural killer T (NKT) cells represent an exceptional lymphocyte population uniting a T cell and natural killer cell-like phenotype with tumor-killing activity. Most NKT cells recognize the antigen-presenting molecule CD1d. NKT cells are classified into type 1 invariant, type 2 diverse and NKT-like cells.

NKT cells have been shown to play an essential role in autoimmune diseases as well as in cancer. NKT cells are present in peripheral blood mononuclear cells or cord blood in low numbers but can be expanded in vitro.

Most clinical trials with NKT cells have been performed with cytokine-induced killer (CIK) cells. CIK cells are licensed, e.g., in Germany.

Due to their easy availability and potent antitumor activity, NKT cells have emerged as a promising immunotherapy approach in oncology and may gain major importance in the prognosis of cancer.

Prof. Dr. Ingo Schmidt-Wolf
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

NKT cells
cytokine-induced killer cells
transplantation
immunotherapy
cancer treatment

Published Papers (4 papers)

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Research

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13 pages, 2414 KiB

Open AccessArticle

Deficiency of Invariant Natural Killer T Cells Does Not Protect Against Obesity but Exacerbates Atherosclerosis in Ldlr^−/− Mice

by Savitha Subramanian, Leela Goodspeed, Shari Wang, Yilei Ding, Kevin D. O’Brien, Godfrey S. Getz, Alan Chait and Catherine A. Reardon

Int. J. Mol. Sci. 2018, 19(2), 510; https://doi.org/10.3390/ijms19020510 - 8 Feb 2018

Cited by 15 | Viewed by 4037

Abstract

Obesity is a chronic inflammatory state characterized by altered levels of adipose tissue immune cell populations. Natural killer T (NKT) cells are CD1d restricted lymphocyte subsets that recognize lipid antigens whose level decreases in obese adipose tissue. However, studies in mice with deficiency or increased levels of NKT cells have yielded contradictory results, so the exact role of these cells in obesity and adipose tissue inflammation is not yet established. We previously showed that Ldlr^−/− mice with excess invariant NKT (iNKT) cells demonstrate significant weight gain, adiposity, metabolic abnormalities, and atherosclerosis. The current study evaluates the effects of NKT cell deficiency on obesity, associated metabolic changes, and atherosclerosis in Jα18^−/−Ldlr^−/− (lacking iNKT cells) and Cd1d^−/−Ldlr^−/− (lacking invariant and type II NKT cells) mice, and control mice were fed an obesogenic diet (high fat, sucrose, cholesterol) for 16 weeks. Contrary to expectations, Ja18^−/−Ldlr^−/− mice gained significantly more weight than Ldlr^−/− or Cd1d^−/−Ldlr^−/− mice, developed hypertriglyceridemia, and had worsened adipose tissue inflammation. All the mice developed insulin resistance and hepatic triglyceride accumulation. Ja18^−/−Ldlr^−/− mice also had increased atherosclerotic lesion area. Our findings suggest that iNKT cells exacerbates the metabolic, inflammatory, and atherosclerotic features of diet-induced obesity. Further work is required to unravel the paradox of an apparently similar effect of iNKT cell surplus and depletion on obesity. Full article

(This article belongs to the Special Issue Natural Killer T (NKT) Cells)

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1628 KiB

Open AccessArticle

CIK Cells and HDAC Inhibitors in Multiple Myeloma

by David Stephan, Hans Weiher and Ingo G.H. Schmidt-Wolf

Int. J. Mol. Sci. 2017, 18(5), 945; https://doi.org/10.3390/ijms18050945 - 29 Apr 2017

Cited by 11 | Viewed by 4244

Abstract

Multiple myeloma is the second most common hematological malignancy. Despite all the progress made in treating multiple myeloma, it still remains an incurable disease. Patients are left with a median survival of 4–5 years. The combined treatment of multiple myeloma with histone deacetylase inhibitors and cytokine-induced killer cells provides a promising targeted treatment option for patients. This study investigated the impact of a combined treatment compared to treatment with histone deacetylase inhibitors. The experiments revealed that a treatment with histone deacetylase (HDAC) inhibitors could reduce cell viability to 59% for KMS 18 cell line and 46% for the U-266 cell line. The combined treatment led to a decrease of cell viability to 33% for KMS 18 and 27% for the U-266 cell line, thus showing a significantly better efficacy than the single treatment. Full article

(This article belongs to the Special Issue Natural Killer T (NKT) Cells)

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Review

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10 pages, 840 KiB

Open AccessReview

The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases

by Alessandra Torina, Giuliana Guggino, Marco Pio La Manna and Guido Sireci

Int. J. Mol. Sci. 2018, 19(2), 440; https://doi.org/10.3390/ijms19020440 - 1 Feb 2018

Cited by 33 | Viewed by 4518

Abstract

Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defense against infections but, on the other hand, their effector functions can be involved in the pathogenesis of several inflammatory disorders due to their exposure to different microbial or self-antigens, respectively. A deep understanding of the biology and functions of type I, II, and NKT-like cells as well as their interplay with cell types acting in innate (neuthrophils, innate lymphoid cells, machrophages, and dendritic cells) and adaptive immunity (CD4⁺,CD8⁺, and double negative T cells) should be important to design potential immunotherapies for infectious and autoimmune diseases. Full article

(This article belongs to the Special Issue Natural Killer T (NKT) Cells)

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14 pages, 774 KiB

Open AccessReview

Innovative Clinical Perspectives for CIK Cells in Cancer Patients

by Martino Introna and Fabio Correnti

Int. J. Mol. Sci. 2018, 19(2), 358; https://doi.org/10.3390/ijms19020358 - 25 Jan 2018

Cited by 46 | Viewed by 7264

Abstract

Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in vitro, following extensive manipulation by Interferon gamma (IFN-γ), OKT3 and Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell-surface markers. CIK cells have a dual “nature”, due to the presence of functional TCR as well as NK molecules, even if the antitumoral activity can be traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In addition to antineoplastic activity in vitro and in several in-vivo models, CIK cells show very limited, if any, GvHD toxicity as well as a strong intratumoral homing. For all such reasons, CIK cells have been proposed and tested in many clinical trials in cancer patients both in autologous and allogeneic combinations, up to haploidentical mismatching. Indeed, genetic modification of CIK cells as well as the possibility of combining them with specific monoclonal antibodies will further expand the possibility of their clinical utilization. Full article

(This article belongs to the Special Issue Natural Killer T (NKT) Cells)

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