Tuning Natural Killer Cell Anti-multiple Myeloma Reactivity by Targeting Inhibitory Signaling via KIR and NKG2A

Mahaweni, Niken M.; Ehlers, Femke A. I.; Bos, Gerard M.J.; Wieten, Lotte

doi:10.3389/fimmu.2018.02848

Cited by 29 publications

(22 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KIRs identify MHC class I molecules (HLA-A, HLA-B, HLA-C) [8], which have two subtypes, KIR2D and KIR3D and can be divided into KIR2DL, KIR3DL, KIR2DS, and KIR3DS according to the length of the amino acid sequence in the cytoplasmic region. KIR2DL and KIR3DL contain immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences that inhibit NK cells, and KIR2DS and KIR3DS combine with immunoreceptor tyrosine-based activation motif (ITAM)-containing DNAX activating protein 12 (DAP12) to activate NK cells [9,10]. NKG2A contains an ITIM sequence, which can inhibit NK cells, whereas NKG2C combines with DAP12 to activate NK cells.…”

Section: Function Of Nkg2d Receptor and Its Ligandsmentioning

confidence: 99%

Natural killer group 2D receptor and its ligands in cancer immune escape

et al. 2019

View full text Add to dashboard Cite

The immune system plays important roles in tumor development. According to the immune-editing theory, immune escape is the key to tumor survival, and exploring the mechanisms of tumor immune escape can provide a new basis for the treatment of tumors. In this review, we describe the mechanisms of natural killer group 2D (NKG2D) receptor and NKG2D ligand (NKG2DL) in tumor immune responses. Natural killer (NK) cells are important cytotoxic cells in the immune system, and the activated NKG2D receptor on the NK cell surface can bind to NKG2DL expressed in tumor cells, enabling NK cells to activate and kill tumor cells. However, tumors can escape the immune clearance mediated by NKG2D receptor/NKG2DL through various mechanisms. The expression of NKG2D receptor on NK cells can be regulated by cells, molecules, and hypoxia in the tumor microenvironment. Tumor cells regulate the expression of NKG2DL at the level of transcription, translation, and post-translation and thereby escape recognition by NK cells. In particular, viruses and hormones have special mechanisms to affect the expression of NKG2D receptor and NKG2DL. Therefore, NKG2D\NKG2DL may have applications as targets for more effective antitumor therapy.

show abstract

Section: Function Of Nkg2d Receptor and Its Ligandsmentioning

confidence: 99%

Natural killer group 2D receptor and its ligands in cancer immune escape

et al. 2019

View full text Add to dashboard Cite

show abstract

“… 90 TIGIT, also known as WUCAM and Vstm3, is an immune checkpoint molecule that inhibits the activation of T cells and NK cells. 7 , 91 – 95 It contains an IgV domain, a transmembrane domain, and an immunoreceptor tyrosine-based inhibitory motif (ITIM). 92 TIGIT has the capacity of disrupting DNAM-1 significantly through cis interactions to form heterodimers.…”

Section: Checkpoint Receptors and Ligands In Nk Cell Dysfunctionmentioning

confidence: 99%

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Cao

Wang

Jin

et al. 2020

Sig Transduct Target Ther

100

View full text Add to dashboard Cite

Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.

show abstract

“…In MM, NK cell function has been shown to be diminished by speci ic factors that are active in the tumor microenvironment (TME) [177]. Also, relatively high levels of HLA molecules are expressed in MM [178]. The recognition of plasma cells in patients with MM by NK cells is regulated by: HLA class I/ HLA-E, NKG2D receptor and possibly NKG2A receptors, and natural cytotoxicity [178][179][180].…”

Section: Preparation Of Nk Cells and Improvement Of Their Potencymentioning

confidence: 99%

“…Also, relatively high levels of HLA molecules are expressed in MM [178]. The recognition of plasma cells in patients with MM by NK cells is regulated by: HLA class I/ HLA-E, NKG2D receptor and possibly NKG2A receptors, and natural cytotoxicity [178][179][180]. HLA class I may be involved in the resistance of myeloma cells to NK cell lysis thus contributing to the immune escape and consequently drug resistance in R/R-MM [181].…”

Section: Preparation Of Nk Cells and Improvement Of Their Potencymentioning

confidence: 99%

“…The excellent safety and feasibility pro iles of NK cells make them interesting candidates in combination therapy with novel agents in order to enhance their clinical ef icacy in the treatment of MM patients [178]. Blockade or inhibition of KIR2D in patients with smoldering myeloma by IPH2101 monoclonal antibody has been shown to enhance NK cell killing of myeloma cell lines [191].…”

Section: Tracing Infused Nk Cellsmentioning

confidence: 99%

See 1 more Smart Citation