NK Cell-Mediated Recall Responses: Memory-Like, Adaptive, or Antigen-Specific?

Stary, Victoria; Stary, Georg

doi:10.3389/fcimb.2020.00208

Cited by 24 publications

(20 citation statements)

References 75 publications

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“…Certain NK cell subsets degranulate more effectively in response to antibody bound targets. These NK cells can be differentiated by the presence of NKG2C and CD57 on the cell surface 47 . However, NKG2C is only found in a subset of donors who are HCMV seropositive, and a proportion of these individuals are NKG2C null due to a deletion in the KLRC2 gene.…”

Section: Resultsmentioning

confidence: 99%

ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies

Fielding

Sabberwal

et al. 2021

Preprint

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SARS-CoV-2 antagonises the cellular interferon response, but whether the virus manipulates cellular immunity is unclear. An unbiased proteomic approach to determine how cell surface protein expression is altered on SARS-CoV-2-infected lung epithelial cells showed downregulation of activating NK cell ligands: B7-H6, MICA, ULBP2, and Nectin1, but no effect on surface MHC-I expression. NK ligand downregulation correlated with a reduction in NK cell activation by infected cells, and was overcome by antibody-dependent NK cell activation (ADNKA). Depletion of spike-specific antibodies confirmed their dominant role in virus neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other viral proteins, including ORF3a, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.

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Section: Resultsmentioning

confidence: 99%

ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies

Fielding

Sabberwal

et al. 2021

Preprint

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“…The enormous potential of innate immunity in GBM has been underlined by multiple studies showing that NK cells represent the most abundant intratumoral lymphocyte population and that GBM cells may be particularly vulnerable to innate effector lymphocytes [23][24][25][26][27][28]. The relevant role of innate immunity in cancer therapy is further supported by recent findings that have confirmed the existence of a subpopulation of NK cells which exhibit antigen or nonantigen specific memory-like functions, revealing that NK cells can possess features analogous to adaptive immunity [29][30][31][32].…”

Section: Introductionmentioning

confidence: 94%

Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study

et al. 2021

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Cancer immunotherapies have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown clinically relevant success in glioblastoma (GBM). This is principally due to the brain’s “immune-privileged” status and the peculiar tumor microenvironment (TME) of GBM characterized by a lack of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Herein, we explore a local mild thermal treatment, generated via cubic-shaped iron oxide magnetic nanoparticles (size ~17 nm) when exposed to an external alternating magnetic field (AMF), to induce immunogenic cell death (ICD) in U87 glioblastoma cells. In accordance with what has been observed with other tumor types, we found that mild magnetic hyperthermia (MHT) modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. At the same time, we demonstrated that mild magnetic hyperthermia on U87 cells has a modulatory effect on the expression of inhibitory and activating NK cell ligands. Interestingly, this alteration in the expression of NK ligands in U87 cells upon MHT treatment increased their susceptibility to NK cell killing and enhanced NK cell functionality. The overall findings demonstrate that mild MHT stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes.

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“…Interestingly, an expanding amount of literature is now describing various NK cell subsets portraying adaptive-like immunological memory and long-lived antigen specificity ( 26 , 27 ). Three main types of such adaptive NK cells have been described to date: (i) NK cells found in the murine liver displaying long-lived memory to haptens and viral antigens; (ii) human NKG2C + and murine Ly49H + NK cells displaying cytomegalovirus (CMV) antigen-specificity and enhanced recall responses; (iii) human and murine cytokine-activated NK cells showing memory-like “trained” features such as enhanced cytotoxicity and production of IFN-γ upon restimulation ( 28 ). A more detailed description of all NK cell subtypes and their distinct characteristics falls outside the scope of this review and can be consulted elsewhere ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Natural Killer Cells in Multiple Sclerosis: Entering the Stage

Beliën

Matthys

2022

Front. Immunol.

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Studies investigating the immunopathology of multiple sclerosis (MS) have largely focused on adaptive T and B lymphocytes. However, in recent years there has been an increased interest in the contribution of innate immune cells, amongst which the natural killer (NK) cells. Apart from their canonical role of controlling viral infections, cell stress and malignancies, NK cells are increasingly being recognized for their modulating effect on the adaptive immune system, both in health and autoimmune disease. From different lines of research there is now evidence that NK cells contribute to MS immunopathology. In this review, we provide an overview of studies that have investigated the role of NK cells in the pathogenesis of MS by use of the experimental autoimmune encephalomyelitis (EAE) animal model, MS genetics or through ex vivo and in vitro work into the immunology of MS patients. With the advent of modern hypothesis-free technologies such as single-cell transcriptomics, we are exposing an unexpected NK cell heterogeneity, increasingly blurring the boundaries between adaptive and innate immunity. We conclude that unravelling this heterogeneity, as well as the mechanistic link between innate and adaptive immune cell functions will lay the foundation for the use of NK cells as prognostic tools and therapeutic targets in MS and a myriad of other currently uncurable autoimmune disorders.

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NK Cell-Mediated Recall Responses: Memory-Like, Adaptive, or Antigen-Specific?

Cited by 24 publications

References 75 publications

ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies

ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies

Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study

Natural Killer Cells in Multiple Sclerosis: Entering the Stage

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