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Natural Killer and NKT Cells in Cancers
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Natural Killer and NKT Cells in Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 12833

Special Issue Editors

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
Dr. Amit Sharma

E-Mail Website
Guest Editor
Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany
Interests: neuro-oncology; glioblastoma; stereotaxic & functional neurosurgery; cancer stem 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 in Cancers”, 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 and Natural Killer and NKT Cells 2020.

Prof. Dr. Ingo Schmidt-Wolf
Dr. Amit Sharma
Guest Editors

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Keywords

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

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Published Papers (4 papers)

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Research

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15 pages, 4405 KiB  
Article
The Correlation between Peripheral Blood Index and Immune Cell Expansion in Vietnamese Elderly Lung Cancer Patients
by Hoang-Phuong Nguyen, Viet Anh Bui, Ai-Xuan Thi Hoang, Phong Van Nguyen, Dac-Tu Nguyen, Hien Thi Mai, Hai-Anh Le, Thanh-Luan Nguyen, Nhung Thi My Hoang, Liem Thanh Nguyen and Xuan-Hung Nguyen
Int. J. Mol. Sci. 2023, 24(5), 4284; https://doi.org/10.3390/ijms24054284 - 21 Feb 2023
Viewed by 2696
Abstract
(1) Background: The dysfunction and reduced proliferation of peripheral CD8+ T cells and natural killer (NK) cells have been observed in both aging and cancer patients, thereby challenging the adoption of immune cell therapy in these subjects. In this study, we evaluated [...] Read more.
(1) Background: The dysfunction and reduced proliferation of peripheral CD8+ T cells and natural killer (NK) cells have been observed in both aging and cancer patients, thereby challenging the adoption of immune cell therapy in these subjects. In this study, we evaluated the growth of these lymphocytes in elderly cancer patients and the correlation of peripheral blood (PB) indices to their expansion. (2) Method: This retrospective study included 15 lung cancer patients who underwent autologous NK cell and CD8+ T cell therapy between January 2016 and December 2019 and 10 healthy individuals. (3) Results: On average, CD8+ T lymphocytes and NK cells were able to be expanded about 500 times from the PB of elderly lung cancer subjects. Particularly, 95% of the expanded NK cells highly expressed the CD56 marker. The expansion of CD8+ T cells was inversely associated with the CD4+:CD8+ ratio and the frequency of PB-CD4+ T cells in PB. Likewise, the expansion of NK cells was inversely correlated with the frequency of PB-lymphocytes and the number of PB-CD8+ T cells. The growth of CD8+ T cells and NK cells was also inversely correlated with the percentage and number of PB-NK cells. (4) Conclusion: PB indices are intrinsically tied to immune cell health and could be leveraged to determine CD8 T and NK cell proliferation capacity for immune therapies in lung cancer patients. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells in Cancers)
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21 pages, 2783 KiB  
Article
Preventing Surgery-Induced NK Cell Dysfunction Using Anti-TGF-β Immunotherapeutics
by Marisa Market, Gayashan Tennakoon, Marlena Scaffidi, David P. Cook, Leonard Angka, Juliana Ng, Christiano Tanese de Souza, Michael A. Kennedy, Barbara C. Vanderhyden and Rebecca C. Auer
Int. J. Mol. Sci. 2022, 23(23), 14608; https://doi.org/10.3390/ijms232314608 - 23 Nov 2022
Viewed by 2500
Abstract
Natural Killer (NK) cell cytotoxicity and interferon-gamma (IFNγ) production are profoundly suppressed postoperatively. This dysfunction is associated with increased morbidity and cancer recurrence. NK activity depends on the integration of activating and inhibitory signals, which may be modulated by transforming growth factor-beta (TGF-β). [...] Read more.
Natural Killer (NK) cell cytotoxicity and interferon-gamma (IFNγ) production are profoundly suppressed postoperatively. This dysfunction is associated with increased morbidity and cancer recurrence. NK activity depends on the integration of activating and inhibitory signals, which may be modulated by transforming growth factor-beta (TGF-β). We hypothesized that impaired postoperative NK cell IFNγ production is due to altered signaling pathways caused by postoperative TGF-β. NK cell receptor expression, downstream phosphorylated targets, and IFNγ production were assessed using peripheral blood mononuclear cells (PBMCs) from patients undergoing cancer surgery. Healthy NK cells were incubated in the presence of healthy/baseline/postoperative day (POD) 1 plasma and in the presence/absence of a TGF-β-blocking monoclonal antibody (mAb) or the small molecule inhibitor (smi) SB525334. Single-cell RNA sequencing (scRNA-seq) was performed on PBMCs from six patients with colorectal cancer having surgery at baseline/on POD1. Intracellular IFNγ, activating receptors (CD132, CD212, NKG2D, DNAM-1), and downstream target (STAT5, STAT4, p38 MAPK, S6) phosphorylation were significantly reduced on POD1. Furthermore, this dysfunction was phenocopied in healthy NK cells through incubation with rTGF-β1 or POD1 plasma and was prevented by the addition of anti-TGF-β immunotherapeutics (anti-TGF-β mAb or TGF-βR smi). Targeted gene analysis revealed significant decreases in S6 and FKBP12, an increase in Shp-2, and a reduction in NK metabolism-associated transcripts on POD1. pSmad2/3 was increased and pS6 was reduced in response to rTGF-β1 on POD1, changes that were prevented by anti-TGF-β immunotherapeutics. Together, these results suggest that both canonical and mTOR pathways downstream of TGF-β mediate phenotypic changes that result in postoperative NK cell dysfunction. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells in Cancers)
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Review

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12 pages, 1445 KiB  
Review
Revising the Landscape of Cytokine-Induced Killer Cell Therapy in Lung Cancer: Focus on Immune Checkpoint Inhibitors
by Rohulla Vaseq, Amit Sharma, Yutao Li and Ingo G. H. Schmidt-Wolf
Int. J. Mol. Sci. 2023, 24(6), 5626; https://doi.org/10.3390/ijms24065626 - 15 Mar 2023
Cited by 7 | Viewed by 3454
Abstract
Undeniably, immunotherapy has markedly improved the survival rate of cancer patients. The scenario is no different in lung cancer, where multiple treatment options are now available and the inclusion of immunotherapy yields better clinical benefits than previously used chemotherapeutic strategies. Of interest, cytokine-induced [...] Read more.
Undeniably, immunotherapy has markedly improved the survival rate of cancer patients. The scenario is no different in lung cancer, where multiple treatment options are now available and the inclusion of immunotherapy yields better clinical benefits than previously used chemotherapeutic strategies. Of interest, cytokine-induced killer (CIK) cell immunotherapy has also taken a central role in clinical trials for the treatment of lung cancer. Herein, we describe the relative success of CIK cell therapy (alone and combined with dendritic cells as DC/CIKs) in lung cancer clinical trials and discuss its combination with known immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Additionally, we provide insights into the findings of several preclinical in vitro/in vivo studies linked to lung cancer. In our opinion, CIK cell therapy, which recently completed 30 years and has been approved in many countries, including Germany, offers tremendous potential for lung cancer. Foremost, when it is optimized on a patient-by-patient basis with special attention to the patient-specific genomic signature. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells in Cancers)
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14 pages, 956 KiB  
Review
Graft-versus-Host Disease Modulation by Innate T Cells
by Ying Fang, Yichen Zhu, Adam Kramer, Yuning Chen, Yan-Ruide Li and Lili Yang
Int. J. Mol. Sci. 2023, 24(4), 4084; https://doi.org/10.3390/ijms24044084 - 17 Feb 2023
Cited by 6 | Viewed by 3625
Abstract
Allogeneic cell therapies, defined by genetically mismatched transplantation, have the potential to become a cost-effective solution for cell-based cancer immunotherapy. However, this type of therapy is often accompanied by the development of graft-versus-host disease (GvHD), induced by the mismatched major histocompatibility complex (MHC) [...] Read more.
Allogeneic cell therapies, defined by genetically mismatched transplantation, have the potential to become a cost-effective solution for cell-based cancer immunotherapy. However, this type of therapy is often accompanied by the development of graft-versus-host disease (GvHD), induced by the mismatched major histocompatibility complex (MHC) between healthy donors and recipients, leading to severe complications and death. To address this issue and increase the potential for allogeneic cell therapies in clinical practice, minimizing GvHD is a crucial challenge. Innate T cells, encompassing subsets of T lymphocytes including mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, and gamma delta T (γδ T) cells, offer a promising solution. These cells express MHC-independent T-cell receptors (TCRs), allowing them to avoid MHC recognition and thus GvHD. This review examines the biology of these three innate T-cell populations, evaluates research on their roles in GvHD modulation and allogeneic stem cell transplantation (allo HSCT), and explores the potential futures for these therapies. Full article
(This article belongs to the Special Issue Natural Killer and NKT Cells in Cancers)
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