Targets Associated to Immuno Cell Types - Natural killer cells
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The Natural killer cells category includes the following Cell Ontology parent terms: |
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Targets Associated to Immuno Cell Types
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ | Download as CSV | ||
| GPCRs | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| GPR65 (Class A Orphans) |
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Tha expression profile of GPR65 suggests an immunological role. In addition, disruption of GPR65 expression leads to reduced eosinophilia in models of allergic airway disease [62] ... | |
| 5-HT1A receptor (5-Hydroxytryptamine receptors) |
The chemoattractant properties of 5-HT on both human and mouse mast cells are mediated by 5-HT1A receptor [64] ... | ||
| CXCR3 (Chemokine receptors) |
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CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes. In the cancer setting cytokines are known to establish an immunosuppressive milieu that is condusive to tumour progression. CXCR3 and its ligands have specifically been identified as being associated with this mechanism in pancreatic ductal adenocarcinoma [18] ... |
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| CB2 receptor (Cannabinoid receptors) |
CB2 receptor expression was detected in human NK cells by single cell RNA-sequencing. |
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CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [84] ... |
| ADGRG1 (Adhesion Class GPCRs) |
ADGRG1 is expressed by mature NK cells and negatively regulates their natural cytotoxicity. |
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An association between ADGRG1 and the tetraspanin CD81, negatively regulates the immediate effector functions (inflammatory cytokine and cytolytic protein production, degranulation, target cell killing) of mature NK cells [23] ... |
| ADGRG5 (Adhesion Class GPCRs) |
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| Ion Channels | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| Orai1 (Orai channels) |
Orai1 is expressed by NK cells and is involved in degranulation and NK cell-mediated cytotoxicity. |
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ORAI1 is the gene that encodes the essential pore-forming subunit of CRAC store-operated Ca2+ entry (SOCE) channels [92] ... |
| TRPM7 (Transient Receptor Potential channels (TRP), ChaK subfamily) |
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Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [88] ... | |
| Enzymes | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| cathepsin C (C1: Papain) |
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Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007). SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [61] ... |
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| FYN proto-oncogene, Src family tyrosine kinase (Src family) |
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Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [86] ... | |
| LCK proto-oncogene, Src family tyrosine kinase (Src family) |
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Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [86] ... | |
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
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LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [41,44,109] ... | |
| YES proto-oncogene 1, Src family tyrosine kinase (Src family) |
Low expression level |
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Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system. |
| TRPM7 (Transient Receptor Potential channels (TRP), ChaK subfamily) |
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Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [88] ... | |
| protein kinase C theta (Delta subfamily) |
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [10] ... | ||
| Catalytic Receptors | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| colony stimulating factor 1 receptor (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
Down-regulated expression measured by Affymetrix GeneChip array, in experiments designed to expand NK cell populations as a potential cancer immunotherapy tool. | Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [2] ... | |
| MER proto-oncogene, tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [12,116] ... | |
| Other Protein Targets | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| CD300a (CD molecules) |
CD300a (IRp60) was originally identified in NK cells. |
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CD300a is a member of the CD300 family of leucocyte surface receptors [14] ... |
| CD2 (CD molecules) |
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [122] ... | ||
| CD38 (Abscisic acid receptor complex, CD molecules) |
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [49] ... | ||
| CD52 (CD molecules) |
CD52 (CAMPATH-1) is a short, glycosylphosphatidylinositol (GPI) anchored peptide expressed on lymphocytes and by cells of the male genital tract. CD52 is required for complement-mediated cell lysis and antibody-mediated cellular cytotoxicity. The approved monoclonal antibody, alemtuzumab ... | ||
| neural cell adhesion molecule 1 (CD56) (CD molecules) |
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CD56 is expressed by neurons, glia, skeletal muscle and natural killer (NK) cells. The CD56bright NK cell subset, predominantly present in secondary lymphoid tissues, are capable of high levels of cytokine production, are enriched at inflammatory sites [30] ... | |
| killer cell lectin like receptor C1 (CD159a) (CD molecules) |
Expression has been reported on NK and T cells from many human cancers. |
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NKG2A (KLRC1; CD159a) acts as an inhibitory checkpoint receptor for HLA-E. NKG2A forms functional heterodimers with CD94 (KLRD1) to form a human leukocyte antigen E (HLA-E) recognition complex on a subset of natural killer (NK) cells and cytotoxic T cells. NKG2A/CD94/HLA-E binding suppresses immune vigilance, and overexpression of HLA-E is used by cancer cells to evade immune recognition and destruction [34,67,75,100] ... |
| CS1 (CD319) (CD molecules) |
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CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions. CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [59] ... |
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| LAG3 (CD223) (Other immune checkpoint proteins, CD molecules) |
LAG3 is expressed on activated human NK cells. |
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Membrane-bound LAG3 (CD223) is a T cell inhibitory co-receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [4,47] ... |
| B7-H3 (CD276) (Other immune checkpoint proteins, CD molecules) |
B7-H3 expression is induced in NK cells by inflammatory cytokines and by phorbol myristate acetate/ionomycin exposure [25]. |
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B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [25,36] ... |
| TIGIT (Other immune checkpoint proteins, Immunoglobulin like domain containing proteins) |
TIGIT is now considered as an alternate inhibitory immune checkpoint protein which may have potential immunotherapeutic potential, particularly in conditions refractory to more established PD-1 checkpoint inhibition. Given its presence on T cells and NK cells, TIGIT offers an intervention point for targeting both the adaptive and innate arms of the immune system. Clinical development of anti-TIGIT monoclonal antibodies is in preliminary stages. Combination therapies with existing immune checkpoint inhibitors are considered particularly promising. MTIG7192A (NCT02794571 ... | ||
| PVR related immunoglobulin domain containing (Other immune checkpoint proteins) |
PVRIG is constitutively expressed by human and murine NK cells. |
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PVRIG has been identified as a novel co-inhibitory immune checkpoint, that is exploited by some cancer cells to evade immune detection [83,119] ... |
| S100 calcium binding protein A11 (EF-hand domain containing proteins) |
S100A11 is a pro-inflammatory calcium-binding protein. Elevated S100A11 has been reported as a marker of disease activity and extramuscular manifestations in inflammatory myopathies [6] ... | ||
| programmed cell death 1 (CD279) (Other immune checkpoint proteins, CD molecules) |
PD-1 is expressed by NK cells; from healthy donors and from most cancer patients [13,33,71,90,113]. Expression is higher in activated NK cells than in exhausted NK cells [52]. In mouse models of cancer, PD-1 blockade elicits a strong NK cell response that is indispensable for the the full therapeutic effect of immunotherapy [52]. |
Immune checkpoint blockade in oncology: Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [85] ... |
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| TIM3 (CD366) (Other immune checkpoint proteins, CD molecules) |
TIM3 is expressed by mature NK cells, including human decidual NK cells. Its expression is upregulated on NK cells from patients with melanoma and lung adenocarcinoma. Elevated expression impairs NK cell effector functions. | TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [82] ... | |
| perforin 1 (Cytolytic pore-forming proteins) |
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Perforin 1 is expressed only in the secretory granules of cytotoxic T cells and natural killer (NK) cells, and it is an essential component of the immune system. These cell types release perforin 1 close to target cells (e.g. virus-infected and neoplastic cells) in process known as the granule exocytosis pathway [31] ... | |
