Emerging Insights into Natural Killer Cell Immunity in Infection and Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 862

Special Issue Editors


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Guest Editor
Indian Institute of Science Education and Research Kolkata, West Bengal, India
Interests: NK cell biology; CAR NK; tumor immunology; immunotherapy; hypoxia; flavivirus; dengue; Zika virus; immunology of pregnancy; granzyme

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Guest Editor
Biomedical and Diagnostic Sciences, The University of Tennessee, Knoxville, TN, USA
Interests: metabolism; T cells; SARS-CoV-2; vaccine development; HSV-1; metabolic therapy; influenza; B cells and antibodies; Treg cells; Th1 cells; innate immune response
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Guest Editor
St. Jude Children’s Research Hospital, Memphis, TN, USA
Interests: T cells; lymphocyte differentiation; autoimmunity; memory-like NK cell; viral infection

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Guest Editor
Sachin Mulik Lab, The University of Texas Health Center, Tyler, TX, USA
Interests: memory like NK cell; viral infection; decidual NK cells; cancer immunology; HSV

Special Issue Information

Dear Colleagues,

Notable attention is deliberated toward understanding natural killer (NK) cells which are the first line of defense against tumor development and viral infections. NK cells, a subset of innate lymphoid cells (ILCs) derived from common lymphocyte progenitors, are potent naturally cytotoxic cells and are known to produce inflammatory cytokines and chemokines. NK cell activity is governed by the collective signals received from cell-surface-activating and inhibitory receptors that orchestrate the delicate balance between immune responses and self-tolerance. Originally discovered as an innate lymphocyte, the entirely novel functions and characteristics of NK cells are just beginning to be unveiled. Recent research has revealed that under certain viral infections or combination of cytokines, stimulation NK cells can exhibit memory or memory-like responses, which were traditionally attributed only to the adaptive immune system.

For decades, scientists have investigated NK cell-based immunotherapies against cancer due to their rapid killing power without any prior sensitization. Initial data from the on-going clinical trials have demonstrated outstanding safety of NK cell infusion, even in the allogeneic setting. Hematopoietic tumor cells often express uniform antigens, making them suitable targets for generating chimeric antigen receptor (CAR) NK cells, such as CD19-CAR NK cells. Additionally, NK cells pose a lower risk of cytokine release syndrome (CRS) compared to CAR T cells. Despite considerable progression in immunotherapies, several challenges must be overcome, such as limited in vivo persistence, limited infiltration into solid tumors and immunoediting of the tumor to evade NK cells. NK cell-derived extracellular vesicles (NK-EVs) containing cytotoxic proteins, cytokines and miRNAs show promise as cancer immunotherapy. Researchers are also actively exploring NK cell-based immunotherapy for treating various viral infections. Ongoing clinical efforts focus on using NK cell products to combat viruses such as HIV, cytomegalovirus (CMV), influenza, BK virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
We invite submissions of research articles, reviews and communications that fall under one of the following umbrellas of research areas:

  • NK cell-directed approaches, including CAR NK cells, to control tumors;
  • NK cell-derived extracellular vesicles and tumor targeting;
  • Memory-like NK cells for tumor and infection control;
  • Approaches to activate and expand NK cells for effective anti-tumor and anti-viral immunity;
  • Tumor microenvironment and NK cells.

Dr. Sumit Sen Santara
Dr. Engin Berber
Dr. Weshely Kujur
Dr. Sachin Mulik
Guest Editors

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Keywords

  • CAR NK cells
  • cancer immunotherapy
  • cell therapy
  • viral infection
  • memory NK cells
  • NK cell targeted therapies
  • NK-immune cell crosstalk
  • exosomes

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Published Papers (1 paper)

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11 pages, 4908 KiB  
Brief Report
The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial
by María Belén Sanchez, Bianca Vasconcelos Cordoba, Carolina Pavlovsky, Beatriz Moiraghi, Ana Ines Varela, Isabel Giere, Mariana Juni, Nicolas Flaibani, José Mordoh, Julio Cesar Sanchez Avalos, Estrella Mariel Levy and Michele Bianchini
Cells 2025, 14(9), 628; https://doi.org/10.3390/cells14090628 - 23 Apr 2025
Viewed by 242
Abstract
Treatment-free remission (TFR) is a key therapeutic goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). While predicting patient outcome remains challenging, different NK cell populations seem crucial. We conducted an immunological sub-study from the Argentina Stop Trial (AST), including [...] Read more.
Treatment-free remission (TFR) is a key therapeutic goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). While predicting patient outcome remains challenging, different NK cell populations seem crucial. We conducted an immunological sub-study from the Argentina Stop Trial (AST), including 46 patients in 2019 (AST I) and 35 new patients between 2022 and 2023 (AST II). To characterize NK cell subsets in patients attempting TFR, peripheral blood mononuclear cell samples were collected before stopping treatment and phenotype and functional characteristics were assessed by flow cytometry. Non-relapsing patients from AST I exhibited NK cell subpopulations with cytomegalovirus-related memory features, high expression of cytotoxicity markers, and robust functionality. Remarkably, though clinical variables were very similar between cohorts, significant immune differences were observed. NK cell percentage and CD16 and CD57 receptor expression levels were significantly reduced in AST II (p = 0.0051; p = 0.0222; p = 0.0033, respectively), whereas NKp46, NKp44 and PD-1 expression levels were significantly increased (p = 0.0081; p < 0.0001; p < 0.0001, respectively). NK cells from AST II patients demonstrated higher overall functionality and more memory-like subpopulations, characterized mainly by the expression of CD57, NKG2C, NKp30 and NKp46 receptors among CD56dim NK cells, also with enhanced functional performance. However, in AST II, we were unable to report an association with clinical outcome. Given the enrollment time of both cohorts and that they appear to be clinically homogeneous, we consider that COVID could be impacting the immune landscape; accordingly, serum samples from AST II, but not AST I, confirmed the presence of anti-SARS-CoV-2 IgG. The influence of the COVID pandemic and the different vaccine platforms on NK cells cannot be underestimated when evaluating the role of the immune system in cancer. Full article
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