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Natural Killer and NKT Cells 2020
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Natural Killer and NKT Cells 2020

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 2020) | Viewed by 16390

Special Issue Editor

Prof. Dr. Ingo Schmidt-Wolf

E-Mail Website
Guest Editor
Department of Integrated Oncology–CIO Bonn, University Hospital Bonn, Bonn, Germany
Interests: immunooncology; cytokine-induced killer cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, “Natural Killer (NK) and Natural Killer T (NKT) Cells 2020”, 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 (NK) as well as Natural Killer T (NKT) cells represent exceptional lymphocyte populations with major tumor-killing activity. NK cells possess activating as well as inhibitory receptors. Most NKT cells recognize the antigen-presenting molecule CD1d. NKT cells are classified into type 1 invariant, type 2 diverse, and NKT-like cells. NK as well as 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, NK and NKT cells have emerged as promising immunotherapeutic approaches in oncology and may become very important in the prognosis of cancer.

More published papers could be found in the closed Special Issue: Natural Killer and NKT Cells

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NK cells
  • NKT cells
  • cytokine-induced killer cells
  • transplantation
  • immunotherapy
  • cancer treatment

Published Papers (4 papers)

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Research

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14 pages, 2227 KiB  
Article
Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds
by Hiromasa Tanno, Emi Kanno, Suzuna Sato, Yu Asao, Mizuki Shimono, Shiho Kurosaka, Yukari Oikawa, Shinyo Ishi, Miki Shoji, Ko Sato, Jun Kasamatsu, Tomomitsu Miyasaka, Hideki Yamamoto, Keiko Ishii, Yoshimichi Imai, Masahiro Tachi and Kazuyoshi Kawakami
Int. J. Mol. Sci. 2021, 22(8), 3931; https://doi.org/10.3390/ijms22083931 - 10 Apr 2021
Cited by 7 | Viewed by 2456
Abstract
Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant [...] Read more.
Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell–deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells 2020)
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20 pages, 3596 KiB  
Article
Increase in Efficacy of Checkpoint Inhibition by Cytokine-Induced-Killer Cells as a Combination Immunotherapy for Renal Cancer
by Mojgan Naghizadeh Dehno, Yutao Li, Hans Weiher and Ingo G.H. Schmidt-Wolf
Int. J. Mol. Sci. 2020, 21(9), 3078; https://doi.org/10.3390/ijms21093078 - 27 Apr 2020
Cited by 18 | Viewed by 3746
Abstract
Cytokine-induced killer (CIK) cells are heterogeneous, major histocompatibility complex (MHC)-unrestricted T lymphocytes that have acquired the expression of several natural killer (NK) cell surface markers following the addition of interferon gamma (IFN-γ), OKT3 and interleukin-2 (IL-2). Treatment with CIK cells demonstrates a practical [...] Read more.
Cytokine-induced killer (CIK) cells are heterogeneous, major histocompatibility complex (MHC)-unrestricted T lymphocytes that have acquired the expression of several natural killer (NK) cell surface markers following the addition of interferon gamma (IFN-γ), OKT3 and interleukin-2 (IL-2). Treatment with CIK cells demonstrates a practical approach in cancer immunotherapy with limited, if any, graft versus host disease (GvHD) toxicity. CIK cells have been proposed and tested in many clinical trials in cancer patients by autologous, allogeneic or haploidentical administration. The possibility of combining them with specific monoclonal antibodies nivolumab and ipilimumab will further expand the possibility of their clinical utilization. Initially, phenotypic analysis was performed to explore CD3, CD4, CD56, PD-1 and CTLA-4 expression on CIK cells and PD-L1/PD-L2 expression on tumor cells. We further treated CIK cells with nivolumab and ipilimumab and measured the cytotoxicity of CIK cells cocultured to renal carcinoma cell lines, A-498 and Caki-2. We observed a significant decrease in viability of renal cell lines after treating with CIK cells (p < 0.0001) in comparison to untreated renal cell lines and anti-PD-1 or anti-CTLA-4 treatment had no remarkable effect on the viability of tumor cells. Using CCK-8, Precision Count Beads™ and Cell Trace™ violet proliferation assays, we proved significant increased proliferation of CIK cells in the presence of a combination of anti-PD-1 and anti-CTLA-4 antibodies compared to untreated CIK cells. The IFN-γ secretion increased significantly in the presence of A-498 and combinatorial blockade of PD-1 and CTLA-4 compared to nivolumab or ipilimumab monotreatment (p < 0.001). In conclusion, a combination of immune checkpoint inhibition with CIK cells augments cytotoxicity of CIK cells against renal cancer cells. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells 2020)
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Review

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17 pages, 1331 KiB  
Review
License to Kill: When iNKT Cells Are Granted the Use of Lethal Cytotoxicity
by Angélica Díaz-Basabe, Francesco Strati and Federica Facciotti
Int. J. Mol. Sci. 2020, 21(11), 3909; https://doi.org/10.3390/ijms21113909 - 30 May 2020
Cited by 26 | Viewed by 5237
Abstract
Invariant Natural Killer T (iNKT) cells are a non-conventional, innate-like, T cell population that recognize lipid antigens presented by the cluster of differentiation (CD)1d molecule. Although iNKT cells are mostly known for mediating several immune responses due to their massive and diverse cytokine [...] Read more.
Invariant Natural Killer T (iNKT) cells are a non-conventional, innate-like, T cell population that recognize lipid antigens presented by the cluster of differentiation (CD)1d molecule. Although iNKT cells are mostly known for mediating several immune responses due to their massive and diverse cytokine release, these cells also work as effectors in various contexts thanks to their cytotoxic potential. In this Review, we focused on iNKT cell cytotoxicity; we provide an overview of iNKT cell subsets, their activation cues, the mechanisms of iNKT cell cytotoxicity, the specific roles and outcomes of this activity in various contexts, and how iNKT killing functions are currently activated in cancer immunotherapies. Finally, we discuss the future perspectives for the better understanding and potential uses of iNKT cell killing functions in tumor immunosurveillance. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells 2020)
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12 pages, 995 KiB  
Review
Extranodal NK/T-Cell Lymphomas: The Role of Natural Killer Cells and EBV in Lymphomagenesis
by Atif Saleem and Yasodha Natkunam
Int. J. Mol. Sci. 2020, 21(4), 1501; https://doi.org/10.3390/ijms21041501 - 22 Feb 2020
Cited by 14 | Viewed by 4231
Abstract
Natural killer (NK) cells are lymphocytes involved in innate and adaptive immune functions. They are the presumed cell of origin of distinct hematolymphoid malignancies, including aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma (ENKTL). This review focuses on the role of NK cells and [...] Read more.
Natural killer (NK) cells are lymphocytes involved in innate and adaptive immune functions. They are the presumed cell of origin of distinct hematolymphoid malignancies, including aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma (ENKTL). This review focuses on the role of NK cells and Epstein–Barr virus (EBV) in ENKTL pathogenesis. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells 2020)
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