Tumor-priming converts NK cells to memory-like NK cells

Pal, Marina; Schwab, Lisa; Yermakova, Anastasiya; Mace, Emily M.; Claus, Rainer; Krahl, Ann-Christin; Woiterski, Jeanette; Hartwig, Udo F.; Orange, Jordan S.; Handgretinger, Rupert; André, Maya C.

doi:10.1080/2162402x.2017.1317411

Cited by 27 publications

(25 citation statements)

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“…However, TIML‐NK cells showed a distinct signature in their transcriptome expression, particularly in the areas of “membrane parts” and “metabolic processes”. Interestingly, gene expression patterns differed between TIML‐ and CIML‐NK cells with the magnitude of regulated genes being distinctly higher in TIML‐NK cells indicating that the functional conversion of TIML‐NK cells is probably more complex than that of CIML‐NK cells . Although not yet formally tested in humans, our preliminary data indicate that the tumor‐induced conversion of NK cells may trigger the emergence and prolonged survival of a so far unacknowledged NK cell differentiation stage that induces GvL effects toward a wide spectrum of tumor diseases (AML, pediatric BCP‐ALL, solid tumors) and which therefore might exhibit beneficial effects in the context of adoptive cell transfer.…”

Section: Introduction To Cellular and Molecular Aspects Of Various Fomentioning

confidence: 87%

“…We earlier provided substantial evidence that priming of naive human NK cells with pediatric acute B cell precursor lymphoblastic leukemia (BCP‐ALL) or acute myeloid leukemia (AML) specimens induces a functional conversion to TIML‐NK cells that display a heightened tumor‐specific cytotoxicity and—in contrast to both CMV‐induced memory NK cells but also human CIML‐NK cells—enhanced perforin synthesis . So far, the intracellular signal transduction mechanisms initiating TIML‐NK cell conversion have remained elusive.…”

Section: Introduction To Cellular and Molecular Aspects Of Various Fomentioning

confidence: 99%

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From bench to bedside: Exploiting memory NK cell responses to leukemia

Schmidt

André

2018

Adv Cell Gene Ther

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The exploitation of natural killer (NK) cell-mediated antileukemic responses in its various facets (emergence of alloreactive NK cells early posttransplantation, cotransfer of mature NK cells during graft manipulation, and adoptive transfer of mature NK cells) has recently come into the focus (reviewed by Handgretinger et al 1 ). Recent publications indicate that NK cells-although belonging per definition to the innate immune system-may acquire under certain conditions (such as high concentrations of cytokines or viral and presumably also tumor antigens) features of adaptive immune cells. 2 Depending on the initiating stimulus, we distinguish these memory NK cells as cytomegalovirus-induced, cytokine-induced, or tumor-induced memory NK cells. Theoretically, these memory NK cells should entail a higher clinical efficacy 1 as they are long-lived, vividly expand, Abstract Natural killer (NK) cells belong to innate lymphoid immune cells that contribute to antitumor responses without requiring prior sensitization. There is strong evidence that NK cells may induce graft-vs-leukemia (GvL) effect without causing graft-vs-host disease (GvHD), and significant efforts are currently undertaken to design and optimize NK cell-based immunotherapeutic strategies against human cancers, particularly against leukemias. However, the results of a number of adoptive NK cell transfer How to cite this article: Schmidt M, André MC. From bench to bedside: Exploiting memory NK cell responses to leukemia.Adv Cell Gene Ther. 2019;2:e28. https://doi.

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Section: Introduction To Cellular and Molecular Aspects Of Various Fomentioning

confidence: 87%

Section: Introduction To Cellular and Molecular Aspects Of Various Fomentioning

confidence: 99%

From bench to bedside: Exploiting memory NK cell responses to leukemia

Schmidt

André

2018

Adv Cell Gene Ther

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“…Memory NK cells have been mainly characterized by the expression of CD49a and CXCR6, are thought to be enriched in the liver and subsequently migrate to the site of infection (Paust et al, 2010;Peng et al, 2013;Reeves et al, 2015;Nikzad et al, 2019). In addition, NK cell memory has been demonstrated to be inducible by cytokine exposure as well as exposure to tumor cells (Cooper et al, 2009;Pal et al, 2017). It is still unclear which NK cell receptors mediate the observed memory responses.…”

Section: A Possible Role For Nkp44-hla-ii Interactions In Nk Cell Memorymentioning

confidence: 99%

Regulation of NK-Cell Function by HLA Class II

Niehrs

Altfeld

2020

Front. Cell. Infect. Microbiol.

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Natural Killer (NK) cells were initially described as part of the innate immune system and characterized by their ability to lyse malignant and virus-infected cells. The cytolytic function of NK cells is tightly controlled by activating and inhibitory receptors expressed on the cell surface. Ligands that interact with a variety of NK-cell receptors include the human leukocyte antigen (HLA) molecules, and the regulation of NK-cell function by HLA class I molecules is well-established. Earlier studies also suggested a role of HLA class II molecules in regulating NK cell activity; yet, interactions between HLA class II molecules and NK cell receptors have not been well-characterized. We recently identified a subset of HLA-DP molecules that can serve as ligands for the natural cytotoxicity receptor NKp44 and activate NK cells. This novel receptor-ligand interaction provides a potential mechanism to explain the strong associations of HLA-DP molecules with HBV infection outcomes, graft-vs.-host disease and inflammatory bowel disease. Furthermore, it adds a new mechanism for NK-cell crosstalk with immune cells expressing HLA class II molecules. In this perspective article, we discuss the potential implications of NK cell receptor interactions with HLA class II molecules for the regulation of immune responses.

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“…Recently, it was found that NK cells have features of adaptive immune cells, particularly the memory-like responses (12)(13)(14)(15)(16)(17)(18). A long-lived murine NK cell population had been reported to be able to self-renew and survive in a lymphopenic environment for more than 6 months (19).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the transcription factor interferon regulatory factor 8 has been found to orchestrate the adaptive NK cell response against CMV infection (25). A recent study showed that naive NK cells could be induced to functionally convert into tumor-induced memory-like NK cells by priming using acute myeloid leukemia or pediatric acute Bcell leukemia specimens (14). These tumor-induced memorylike NK cells exhibit certain similarities to cytokine-induced memory-like NK cells and CMV-specific NK cells; however, more importantly, they show significant differences, such as higher tumor-specific cytotoxicity and increased synthesis of perforins, but not IFN-γ secretion.…”

Section: Introductionmentioning

confidence: 99%

Targeting Natural Killer Cells for Tumor Immunotherapy

Zhang

Shi

2020

Front. Immunol.

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Natural killer (NK) cells are important innate cytotoxic lymphocytes with a rapid and efficient capacity to recognize and kill tumor cells. In recent years, adoptive transfer of autologous-or allogeneic-activated NK cells has become a promising cellular therapy for cancer. However, the therapeutic efficiency is encouraging in hematopoietic malignancies, but disappointing in solid tumors, for which the use of NK-cell-based therapies presents considerable challenges. It is difficult for NK cells to traffic to, and infiltrate into, tumor sites. NK cell function, phenotype, activation, and persistence are impaired by the tumor microenvironment, even leading to NK cell dysfunction or exhaustion. Many strategies focusing on improving NK cells' durable persistence, activation, and cytolytic activity, including activation with cytokines or analogs, have been attempted. Modifying them with chimeric antigen receptors further increases the targeting specificity of NK cells. Checkpoint blockades can relieve the exhausted state of NK cells. In this review, we discuss how the cytolytic and effector functions of NK cells are affected by the tumor microenvironment and summarize the various immunotherapeutic strategies based on NK cells. In particular, we discuss recent advances in overcoming the suppressive effect of the tumor microenvironment with the aim of enhancing the clinical outcome in solid tumors treated with NK-cell-based immunotherapy.

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Tumor-priming converts NK cells to memory-like NK cells

Cited by 27 publications

References 50 publications

From bench to bedside: Exploiting memory NK cell responses to leukemia

From bench to bedside: Exploiting memory NK cell responses to leukemia

Regulation of NK-Cell Function by HLA Class II

Targeting Natural Killer Cells for Tumor Immunotherapy

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