The Role of Activating and Inhibitory NK Cell Receptors in Antitumor Immune Response

Konjević, Gordana; Vuletić, Ana; Martinović, Katarina Mirjačić; Džodić, Radan

doi:10.5772/intechopen.69729

Cited by 11 publications

(14 citation statements)

References 76 publications

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“…NK cells mediate their anti-tumor immunity based on the net balance of inhibitory and activating receptors (Figure 1) [17,18]. Target cell killing mediated by NK cells does not occur by default in the absence of inhibitory receptor engagement, but requires the presence of activating receptors to stimulate cytotoxicity.…”

Section: Immunobiology Of Target Recognition By Natural Killer Cellsmentioning

confidence: 99%

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Lupo

Matosevic

2019

Cancers

148

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Natural killer (NK) cells are attractive within adoptive transfer settings in cancer immunotherapy due to their potential for allogeneic use; their alloreactivity is enhanced under conditions of killer immunoglobulin-like receptor (KIR) mismatch with human leukocyte antigen (HLA) ligands on cancer cells. In addition to this, NK cells are platforms for genetic modification, and proliferate in vivo for a shorter time relative to T cells, limiting off-target activation. Current clinical studies have demonstrated the safety and efficacy of allogeneic NK cell adoptive transfer therapies as a means for treatment of hematologic malignancies and, to a lesser extent, solid tumors. However, challenges associated with sourcing allogeneic NK cells have given rise to controversy over the contribution of NK cells to graft-versus-host disease (GvHD). Specifically, blood-derived NK cell infusions contain contaminating T cells, whose activation with NK-stimulating cytokines has been known to lead to heightened release of proinflammatory cytokines and trigger the onset of GvHD in vivo. NK cells sourced from cell lines and stem cells lack contaminating T cells, but can also lack many phenotypic characteristics of mature NK cells. Here, we discuss the available published evidence for the varying roles of NK cells in GvHD and, more broadly, their use in allogeneic adoptive transfer settings to treat various cancers.

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Section: Immunobiology Of Target Recognition By Natural Killer Cellsmentioning

confidence: 99%

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Lupo

Matosevic

2019

Cancers

148

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“…There are two main inhibitory receptors, the killer immunoglobulin-like receptor (KIR) family, which can bind HLA-class I, and the heterodimeric receptors CD94-NKG2A/B, which recognize HLA-E [124,126,127]. In malignancies, activating killer cell immunoglobulin-like receptors (KARs) are often decreased, while the expression of the most prominent inhibitory NK cell receptors, KIRs and CD94/NKG2A, may occasionally increase [128,129]. Remarkably, NK cell activation is determined by the balance of inhibitory and activating receptor stimulation [129,130].…”

Section: Nk Cell Educationmentioning

confidence: 99%

“…Remarkably, NK cell activation is determined by the balance of inhibitory and activating receptor stimulation [129,130]. Indeed, in the absence of inhibitory interactions, NK cells kill target cells and produce cytokines in great quantities [128]. By secreting large amounts of cytokines and chemokines, mature NK cells can not only directly kill target cells but can also elicit other immune cells, including monocytes, DCs, and T cells.…”

Section: Nk Cell Educationmentioning

confidence: 99%

An Alternative Cell Therapy for Cancers: Induced Pluripotent Stem Cell (iPSC)-Derived Natural Killer Cells

et al. 2021

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Cell therapy is usually defined as the treatment or prevention of human disease by supplementation with cells that have been selected, manipulated, and pharmacologically treated or altered outside the body (ex vivo). Induced pluripotent stem cells (iPSCs), with their unique characteristics of indefinite expansion in cultures and genetic modifications, represent an ideal cell source for differentiation into specialized cell types. Cell therapy has recently become one of the most promising therapeutic approaches for cancers, and different immune cell types are selected as therapeutic platforms. Natural killer (NK) cells are shown to be effective tumor cell killers and do not cause graft-vs-host disease (GVHD), making them excellent candidates for, and facilitating the development of, “off-the-shelf” cell therapies. In this review, we summarize the progress in the past decade in the advent of iPSC technology and review recent developments in gene-modified iPSC-NK cells as readily available “off-the-shelf” cellular therapies.

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“…In this sense a typical example is a family of nectin-binding adhesion molecules that includes activating receptor CD226 (DNAX accessory molecule-1, DNAM1), and its inhibitory counterparts CD96 [T cell-activated increased late expression (TACTILE)] and T-cell immunoglobulin and ITIM domain (TIGIT) receptors. These receptors bind nectin proteins, CD112 (nectin-2), and CD155 [poliovirus receptor (PVR)] and have been recently identified as crucial regulators of NK cell function ( Martinet and Smyth, 2015 ; Konjević et al, 2017a ).…”

Section: Introductionmentioning

confidence: 99%

“…NK cells are present in peripheral blood, lymph nodes, and may owing to their unique ability to display MHC I-independent cytotoxicity play an important role in immunosurveillance of disseminated tumor cells in tumor draining lymph nodes ( Vuletić et al, 2013 ; Ali et al, 2014 ) and in eradication of distant metastasis ( Lakshmikanth et al, 2009 ; Lorenzo-Herrero et al, 2018 ). However, in malignancies tumor-derived immunosuppressive factors often affect the expression of NK cell receptors that together with cytolytic molecule dysregulation, leads to inhibition of NK cell function ( Konjević et al, 2012 , 2017a ).…”

Section: Introductionmentioning

confidence: 99%

Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer

Vuletić

Martinović

Miletić

et al. 2021

Front. Cell Dev. Biol.

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Tumor cells undergoing epithelial to mesenchymal transition (EMT) and immune cells in tumor microenvironment (TME) reciprocally influence each other. Immune cells, by supplying TME with bioactive molecules including cytokines, chemokines, enzymes, metabolites, and by physical interactions with tumor cells via their receptors, represent an important factor that affects EMT. Chronical inflammation in TME favorizes tumor growth and invasiveness and stimulates synthesis of EMT promoting transcription factors. Natural killer (NK) cells, owing to their unique ability to exert cytotoxic function independent of major histocompatibility (MHC)-mediated antigen presentation, play a significant role in the control of metastasis in colorectal cancer (CRC). Although, the cross-talk between immune cells and tumor cells in general favors the induction of EMT and inhibition of antitumor immune responses, there are some changes in the immunogenicity of tumor cells during EMT of CRC cells that increase their susceptibility to NK cell cytotoxic lysis. However, suppressive TME downmodulates the expression of activating NK cell receptors, decreases the expression of activating and increases the expression of inhibitory NK cell ligands on tumor cells, and impairs NK cell metabolism that altogether negatively affects the overall NK cell function. Furthermore, process of EMT is often associated with increased expression of programmed cell death ligand (PD-L) and expression of immune checkpoint molecules PD-1, TIGIT, and TIM3 on functionally exhausted NK cells in TME in CRC. In this review we discuss modalities of cross-talk between tumor cells and NK cells, with regard of EMT-driven changes.

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The Role of Activating and Inhibitory NK Cell Receptors in Antitumor Immune Response

Cited by 11 publications

References 76 publications

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

An Alternative Cell Therapy for Cancers: Induced Pluripotent Stem Cell (iPSC)-Derived Natural Killer Cells

Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer

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