Biological and Clinical Significance of Human NKRP1A/LLT1 Receptor/Ligand Interactions

Białoszewska, Agata; Malejczyk, Jacek

doi:10.1615/critrevimmunol.2019029559

Cited by 19 publications

(17 citation statements)

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“…NKRP1A (CD161), a C-type lectin-like inhibitory receptor that recognizes lectin-like transcript 1 (LLT1), can be considered a putative checkpoint receptor. Indeed, since LLT1 is expressed by different tumors, including B-cell non-Hodgkin’s lymphomas (NHLs) [96], this receptor/ligand pair may play a role in tumor escape from NK cell control. Moreover, blocking NKRP1A/LLT1 interaction increases NK cell-mediated secretion of IFN-γ and killing of NHL cell lines.…”

Section: Nk Cell Receptorsmentioning

confidence: 99%

NK Cell-Based Immunotherapy for Hematological Malignancies

Sivori

Meazza

Quintarelli

et al. 2019

JCM

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Natural killer (NK) lymphocytes are an integral component of the innate immune system and represent important effector cells in cancer immunotherapy, particularly in the control of hematological malignancies. Refined knowledge of NK cellular and molecular biology has fueled the interest in NK cell-based antitumor therapies, and recent efforts have been made to exploit the high potential of these cells in clinical practice. Infusion of high numbers of mature NK cells through the novel graft manipulation based on the selective depletion of T cells and CD19 + B cells has resulted into an improved outcome in children with acute leukemia given human leucocyte antigen (HLA)-haploidentical hematopoietic transplantation. Likewise, adoptive transfer of purified third-party NK cells showed promising results in patients with myeloid malignancies. Strategies based on the use of cytokines or monoclonal antibodies able to induce and optimize NK cell activation, persistence, and expansion also represent a novel field of investigation with remarkable perspectives of favorably impacting on outcome of patients with hematological neoplasia. In addition, preliminary results suggest that engineering of mature NK cells through chimeric antigen receptor (CAR) constructs deserve further investigation, with the goal of obtaining an "off-the-shelf" NK cell bank that may serve many different recipients for granting an efficient antileukemia activity.

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Section: Nk Cell Receptorsmentioning

confidence: 99%

NK Cell-Based Immunotherapy for Hematological Malignancies

Sivori

Meazza

Quintarelli

et al. 2019

JCM

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“…CD161 can bind to C-type lectin-like transcript-1 (LLT-1) expressed by several hematological malignancies, including Burkitt lymphoma, FL, and DLBCL [ 209 , 210 ]. It is of note that the CD161/LLT1 interaction in NK cells impairs cytokines secretion and cytotoxic activity, thus decreasing tumor susceptibility to NK cells [ 209 , 210 , 211 ]. The negative role of LLT-1 on NK cell functions is confirmed by the fact that the blockade of CD161/LLT-1 axis increases the NK cell-mediated secretion of IFN-γ and the killing of tumor cells [ 210 , 211 ].…”

Section: Current Advanced Therapy In Hematological Malignanciesmentioning

confidence: 99%

Checkpoint Inhibitors and Engineered Cells: New Weapons for Natural Killer Cell Arsenal Against Hematological Malignancies

Giuliani

Poggi

2020

Cells

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Natural killer (NK) cells represent one of the first lines of defense against malignant cells. NK cell activation and recognition are regulated by a balance between activating and inhibitory receptors, whose specific ligands can be upregulated on tumor cells surface and tumor microenvironment (TME). Hematological malignancies set up an extensive network of suppressive factors with the purpose to induce NK cell dysfunction and impaired immune-surveillance ability. Over the years, several strategies have been developed to enhance NK cells-mediated anti-tumor killing, while other approaches have arisen to restore the NK cell recognition impaired by tumor cells and other cellular components of the TME. In this review, we summarize and discuss the strategies applied in hematological malignancies to block the immune check-points and trigger NK cells anti-tumor effects through engineered chimeric antigen receptors.

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“…The recognition of target cells by NK cells involves the participation of some adhesion molecules [53,54] as well as a battery of different stimulatory and inhibitory receptors belonging to several different receptor families, such as killer immunoglobulin-like receptors (KIRs) [55,56,57], leucocyte immunoglobulin-like receptors (LILRs) [58,59], natural cytotoxicity receptors (NCRs) [60,61], and killer cell lectin-like receptors (KLRs) comprising CD94/natural killer G2 (NKG2) [62,63] and natural killer receptor P1 (NKRP1) subfamilies [64,65,66]. It appears that triggering of a NK cell cytotoxic reaction is determined by a balance between the activation and inhibition signals [67].…”

Section: Phenotype and Function Of Nk Cellsmentioning

confidence: 99%

“…The inhibitory NKRP1A receptor belonging to KLR family and being activated by lectin-like transcript 1 (LLT1) ligand appears to be another important NK cell checkpoint [65,66]. However, the authors were unable to find any information on a putative role of NKRP1A/LLT1 checkpoint in the pathogenesis of endometriosis.…”

Section: Expression Of Nk Cell Receptors and Their Ligands In Patimentioning

confidence: 99%

“…However, the authors were unable to find any information on a putative role of NKRP1A/LLT1 checkpoint in the pathogenesis of endometriosis. This system may be of special interest because it has been found that the expression of LLT1 protects many different tumor cells from lysis by NK cells and the downregulation of this molecule resulted in the restoration of target cell killing [66]. A similar effect was also observed following the downregulation of NKRP1A expression in NK cells, e.g., by their stimulation with IL-2 [117].…”

Section: Expression Of Nk Cell Receptors and Their Ligands In Patimentioning

confidence: 99%

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NK Cells as Potential Targets for Immunotherapy in Endometriosis

Ścieżyńska

Komorowski

Soszyńska

et al. 2019

JCM

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Endometriosis is a common gynecological disease defined by the presence of endometrial-like tissue outside the uterus, most frequently on the pelvic viscera and ovaries, which is associated with pelvic pains and infertility. It is an inflammatory disorder with some features of autoimmunity. It is accepted that ectopic endometriotic tissue originates from endometrial cells exfoliated during menstruation and disseminating into the peritoneum by retrograde menstrual blood flow. It is assumed that the survival of endometriotic cells in the peritoneal cavity may be partially due to their abrogated elimination by natural killer (NK) cells. The decrease of NK cell cytotoxic activity in endometriosis is associated with an increased expression of some inhibitory NK cell receptors. It may be also related to the expression of human leukocyte antigen G (HLA-G), a ligand for inhibitory leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) receptors. The downregulated cytotoxic activity of NK cells may be due to inhibitory cytokines present in the peritoneal milieu of patients with endometriosis. The role of NK cell receptors and their ligands in endometriosis is also confirmed by genetic association studies. Thus, endometriosis may be a subject of immunotherapy by blocking NK cell negative control checkpoints including inhibitory NK cell receptors. Immunotherapies with genetically modified NK cells also cannot be excluded.

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Biological and Clinical Significance of Human NKRP1A/LLT1 Receptor/Ligand Interactions

Cited by 19 publications

References 0 publications

NK Cell-Based Immunotherapy for Hematological Malignancies

NK Cell-Based Immunotherapy for Hematological Malignancies

Checkpoint Inhibitors and Engineered Cells: New Weapons for Natural Killer Cell Arsenal Against Hematological Malignancies

NK Cells as Potential Targets for Immunotherapy in Endometriosis

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