Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Bigley, Austin B.; Rezvani, Katayoun; Shah, Nina; Sekine, Takuya; Balneger, Natasja; Pistillo, Mira; Agha, Nadia H.; Kunz, Hawley; O’Connor, Daniel P.; Bollard, Catherine M.; Simpson, Richard J.

doi:10.1111/cei.12785

Cited by 49 publications

(71 citation statements)

References 54 publications

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“…Other groups found impaired degranulation and reduced cytokine production by NKG2C + HCMV-adaptive NK cells in response to K562 targets [37, 40]. These differences may potentially be explained by variable expression of the NKG2C ligand HLA-E [45]. Regardless, adaptive NK cells (NKG2C + or NKG2C - ) consistently had enhanced responses to FcγRIIIa cross-linking and antibody-triggered responses to tumor targets (Figure 1) [36, 37, 40].…”

Section: Anti-tumor Responses Of Memory Nk Cellsmentioning

confidence: 98%

Harnessing NK Cell Memory for Cancer Immunotherapy

Fehniger

Cooper

2016

Trends in Immunology

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Due to their ability to kill cancer cells and produce pro-inflammatory cytokines, natural killer (NK) cells have long been of clinical interest for their anti-tumor properties. The recent discovery of NK cell memory demonstrates that NK cell functions, and potentially anti-tumor responses, can be enhanced long-term. Following non-specific activation with the cytokines IL-12, IL-15, and IL-18 or in response to antigens or cytomegalovirus (CMV), human and mouse NK cells exhibit stable, enhanced functional responses with phenotypic and molecular changes. Here we review mechanisms driving differentiation of NK cell memory-like properties, evidence for anti-tumor activity, and the challenges and opportunities in harnessing these for cancer immunotherapy.

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Section: Anti-tumor Responses Of Memory Nk Cellsmentioning

confidence: 98%

Harnessing NK Cell Memory for Cancer Immunotherapy

Fehniger

Cooper

2016

Trends in Immunology

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“…Besides antigenicity, viral proteins can also influence the interaction between tumor and immune system through several other mechanisms. For example, patients with latent cytomegalovirus may have increased anti-tumor cytotoxic activity of natural killer cells (38). Likewise, EBV may drive the expression of PD-L1 (independent of 9p24.1 amplification) in Hodgkin’s lymphoma and other EBV+ cancers (39,40).…”

Section: An Understanding Of the Challenges And Limitations Unique Tomentioning

confidence: 99%

The Challenge for Development of Valuable Immuno-oncology Biomarkers

Mehnert

Monjazeb

Beerthuijzen

et al. 2017

Clinical Cancer Research

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The development of immunotherapy is an important breakthrough for the treatment of cancer, with anti-tumor efficacy observed in a wide variety of tumors. To optimize immunotherapy use, approaches must be developed to identify which patients are likely to achieve benefit. To minimize therapeutic toxicities and costs, understanding the ideal choice and sequencing of the numerous immuno-oncology agents available for individual patients is thus critical, but fraught with challenges. The immune tumor microenvironment (TME) is a unique aspect of the response to immuno-oncology agents and measurement of single biomarkers does not adequately capture these complex interactions. Therefore, multiple potential biomarkers are likely needed. Current candidates in this area include PD-L1 expression, CD8+ tumor infiltrating lymphocytes, tumor mutation load and neoantigen burden, immune related gene signatures and multiplex immunohistochemical assays that examine the pharmacodynamic and spatial interactions of the TME. The most fruitful investigations are likely to use several techniques to predict response and interrogate mechanisms of resistance. Immuno-oncology biomarker research must employ validated assays to ask focused research questions utilizing clinically annotated tissue collections and biomarker focused clinical trial designs to investigate specific endpoints. Real time input from patients and their advocates into biomarker discovery is necessary to ensure that the investigations pursued will improve both clinical outcomes and quality of life. We herein provide a framework of recommendations to guide the search for immuno-oncology biomarkers of value.

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“…But at the same time researchers are paying greater attention to cell populations of in-born immunity [1,15,19,27]. Thus, NK (natural killers)-cell populations (hereinafter called NK-populations) play a significant role as regards developing anti-body immunity in children [6,26]. Intercellular communications with NK-populations participation are given special attention due to their anti-microbe, anti-virus, and anti-tumor potential.…”

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confidence: 99%

NK-cells that identify glycopatterns and their anti-tumor potential against a background of epidemically significant viral infections

Lakhtin¹,

Lakhtin²,

Алешкин³

et al. 2019

Health Risk Analysis

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Risks related to tumors development against a background of viral infections as well as factors that determine such risks or reduce them have not been examined profoundly so far. Our research goal was to accomplish a scientific review of research on a potential possessed by populations of lectin NK-cells (natural killers) in a body; such populations can have variable sets of lectin and other functionally significant cell surface receptors against tumors in a situation when viruses, including epidemically significant ones, penetrate a body. It is shown that cofunctioning of various receptors and their ligands that redistribute cytokines (glycopattern-identifying lectin (basis) receptors, Ig-similar receptors, cytotoxic receptors, and other effector (adjusting) receptors) plays a significant role in intercellular communications and effects produced by NK-populations. NK-populations network is a promising resource for body protection and it should be taken into account when developing new anti-tumor and anti-viralpreventive and medical strategies. When certain NK-populations with protective functions are absent in a body, it can be considered a new multi-factor risk of viral and oncologic diseases in an individual or a contingent living in a specific region. The reviewed data can be applied to develop new anti-tumor and anti-viral medications and vaccines as well as medical strategies. Probiotic lectins are promising ligands of intercellular communications associated with immune surveillance. Read online __________________________  Lakhtin M.V.

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Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

Cited by 49 publications

References 54 publications

Harnessing NK Cell Memory for Cancer Immunotherapy

Harnessing NK Cell Memory for Cancer Immunotherapy

The Challenge for Development of Valuable Immuno-oncology Biomarkers

NK-cells that identify glycopatterns and their anti-tumor potential against a background of epidemically significant viral infections

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