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NKG2D Receptor and Its Ligands in Host Defense
Open accessAbstract
NKG2D is an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, and subsets of CD4+ T cells, invariant NKT cells (iNKT), and γδ T cells. In humans, NKG2D transmits signals by its association with the DAP10 adapter subunit, and in mice alternatively spliced isoforms transmit signals either using DAP10 or DAP12 adapter subunits. Although NKG2D is encoded by a highly conserved gene (KLRK1) with limited polymorphism, the receptor recognizes an extensive repertoire of ligands, encoded by at least eight genes in humans (MICA, MICB, RAET1E, RAET1G, RAET1H, RAET1I, RAET1L, and RAET1N), some with extensive allelic polymorphism. Expression of the NKG2D ligands is tightly regulated at the level of transcription, translation, and posttranslation. In general, healthy adult tissues do not express NKG2D glycoproteins on the cell surface, but these ligands can be induced by hyperproliferation and transformation, as well as when cells are infected by pathogens. Thus, the NKG2D pathway serves as a mechanism for the immune system to detect and eliminate cells that have undergone “stress.” Viruses and tumor cells have devised numerous strategies to evade detection by the NKG2D surveillance system, and diversification of the NKG2D ligand genes likely has been driven by selective pressures imposed by pathogens. NKG2D provides an attractive target for therapeutics in the treatment of infectious diseases, cancer, and autoimmune diseases. Cancer Immunol Res; 3(6); 575–82. ©2015 AACR.
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“Remarkably, the candidate signature gene RAET1G is one of the few genes that could encode a ligand recognized by NKG2D proteins in response to stress and infections (Eagle and Trowsdale, 2007; Tomasec et al., 2007; Lanier, 2015).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Lanier, 2015
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Cites
Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.
Bauer, S., Groh, V., Wu, J., Steinle, A., Phillips, J., Lanier, L., & Spies, T. (1999) · Science · doi:10.1126/science.285.5428.727 · Cited by 3,272 · cited 2×
“Although NKG2D is expressed constitutively on essentially all resting human NK cells and CD8þ T cells (14), engagement of NKG2D alone is insufficient to trigger cell-mediated cytotoxicity or cytokine production (12, 40), although the simultaneous engagement of NKG2D and other "costimulatory" receptors, such as CD335 (…”
BackgroundSelf-citationTumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation
Groh, V., Wu, J. D., Yee, C., & Spies, T. (2002) · Nature · doi:10.1038/nature01112 · Cited by 1,674 · cited 1×
“These include systemic release of NKG2D ligands by tumors in cancer patients (65, 66).”
BackgroundCosman, D., Müllberg, J., Sutherland, C. L., Chin, W. A., Armitage, R., Fanslow, W., Kubin, M., & Chalupny, N. (2001) · Immunity · doi:10.1016/s1074-7613(01)00095-4 · Cited by 1,394 · cited 11×
“MICA, MICB, RAET1E (ULBP4), and RAET1G (ULBP5) are transmembrane-anchored glycoproteins, whereas RAET1I (ULBP1), RAET1H (ULBP2), RAET1N (ULBP3), and RAET1L (ULBP6) are glycophosphatidylinositol (GPI)-anchored, although RAET1H (ULBP2) may be expressed in both transmembraneanchored and GPI-anchored forms (28), and RAET1…”
BackgroundInfluentialThe DNA damage pathway regulates innate immune system ligands of the NKG2D receptor
Gasser, S., Orsulic, S., Brown, E. J., & Raulet, D. H. (2005) · Nature · doi:10.1038/nature03884 · Cited by 1,308 · cited 1×
“In some cases, ligands may be induced due to the genomic instability of the transformed cells, resulting in activation of the ATM and ATR DNA repair pathways (61).”
BackgroundAn activating immunoreceptor complex formed by NKG2D and DAP10.
Wu, J., Song, Y., Bakker, A. B., Bauer, S., Spies, T., Lanier, L., & Phillips, J. (1999) · Science · doi:10.1126/science.285.5428.730 · Cited by 1,168 · cited 6×
“org Cancer Immunol Res; 3(6) June 2015 579”
BackgroundInfluentialSelf-citationRae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity
Diefenbach, A., Jensen, E. R., Jamieson, A. M., & Raulet, D. H. (2001) · Nature · doi:10.1038/35093109 · Cited by 1,083 · cited 1×
“Studies using transplantable mouse tumors have demonstrated that expression of an NKG2D ligand is sufficient to cause rejection of the tumor (62, 63).”
BackgroundImmunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells
Lanier, L. L., Corliss, B. C., Wu, J., Leong, C. C., & Phillips, J. H. (1998) · Nature · doi:10.1038/35642 · Cited by 907 · cited 1×
“Association of NKG2D with DAP12 versus DAP10 has significant consequences for signal transduction in that DAP12 possesses a canonical immunotyrosine-based activation motif (ITAM), which recruits Syk and ZAP70 tyrosine kinases (7), whereas DAP10 has a YINM motif, which recruits a p85 PI3 kinase and Vav-1 signaling comp…”
BackgroundSelf-citationMeresse, B., Chen, Z., Ciszewski, C., Tretiakova, M., Bhagat, G., Krausz, T., Raulet, D., Lanier, L., Groh, V., Spies, T., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.06.020 · Cited by 901 · cited 1×
“NKG2D-dependent, TCR-independent cytolytic activity has also been observed in intraepithelial intestinal CD8þ T cells isolated from patients with celiac disease, possibly due to exposure to excess IL15 in the inflamed tissue (43).”
BackgroundSelf-citationBryceson, Y., March, M., Ljunggren, H., & Long, E. O. (2006) · Blood · doi:10.1182/blood-2005-04-1351 · Cited by 885 · cited 1×
“Although NKG2D is expressed constitutively on essentially all resting human NK cells and CD8þ T cells (14), engagement of NKG2D alone is insufficient to trigger cell-mediated cytotoxicity or cytokine production (12, 40), although the simultaneous engagement of NKG2D and other "costimulatory" receptors, such as CD335 (…”
BackgroundDiefenbach, A., Jamieson, A. M., Liu, S. D., Shastri, N., & Raulet, D. H. (2000) · Nature Immunology · doi:10.1038/77793 · Cited by 878
Research works printed but not linked: 2
- Castriconi, 2003, Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells, Proc Natl Acad Sci U S A, 100, 4120, 10.1073/pnas.0730640100 · DOI
- Spear, 2013, NKG2D ligands as therapeutic targets, Cancer Immun, 13, 8
Cited by
Sorted by citations
Items 101–200 of 516
Campos, T. M., Novais, F. O., Saldanha, M., Costa, R. S., Lordelo, M. J., Celestino, D., Sampaio, C., Tavares, N., Arruda, S., Machado, P., et al. (2019) · Journal of Infectious Diseases · doi:10.1093/infdis/jiz538 · Cited by 51
“This receptor binds to MICA/B surface receptors on target cells [21].”
BackgroundXu, L.-J., Ma, Q., Zhu, J., Li, J., Xue, B., Gao, J., Sun, C.-Y., Zang, Y.-C., Zhou, Y.-B., Yang, D.-R., et al. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8905 · Cited by 51
“Firstly we examined the expression of ligands of NKG2D, a major activating receptor of NK cells, which include the ULBP family (ULBP-1, ULBP-2 and ULBP-3) and MICA/MICB (44).”
Target tumor microenvironment by innate T cells
Li, Y.-R., Wilson, M., & Yang, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.999549 · Cited by 56
“Recognition of NK receptor ligands on TAMs activates Perforin/Granzyme-mediated lysis and IFNg secretion, suppressing the pro-tumoral environment generated by TAMs (46, 49).”
BackgroundRussick, J., Torset, C., Hemery, E., & Cremer, I. (2020) · Seminars in Immunology · doi:10.1016/j.smim.2020.101407 · Cited by 62
Costanzo, M. C., Kim, D., Creegan, M., Lal, K. G., Ake, J., Currier, J., Streeck, H., Robb, M., Michael, N., Bolton, D., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03618-w · Cited by 49
NKG2D: A versatile player in the immune system.
Jelenčić, V., Lenartić, M., Wensveen, F. M., & Polić, B. (2017) · Immunology Letters · doi:10.1016/j.imlet.2017.04.006 · Cited by 49
Exploiting natural killer group 2D receptors for CAR T-cell therapy
Demoulin, B., Cook, W. J., Murad, J., Graber, D. J., Sentman, M.-L., Lonez, C., Gilham, D. E., Sentman, C. L., & Agaugué, S. (2017) · Future Oncology · doi:10.2217/fon-2017-0102 · Cited by 58
Genetic susceptibility to EBV infection: insights from inborn errors of immunity
Tangye, S. (2020) · Human Genetics · doi:10.1007/s00439-020-02145-3 · Cited by 48
“1), a heavily glycosylated C-type lectin (Lanier 2015).”
BackgroundInfluentialExploiting NK Cell Surveillance Pathways for Cancer Therapy
Barrow, A., & Colonna, M. (2019) · Cancers · doi:10.3390/cancers11010055 · Cited by 48
“For example, human CMV encodes several molecules and microRNAs that prevent the expression of NKG2DLs at the infected cell-surface [132,139] and tumours can express proteases that cleave NKG2DLs from the cell-surface, or release cytokines, such as TGF-β, that downregulate NKG2D, or simply switch off the expression of…”
BackgroundFan, J., Shi, J.-W., Zhang, Y., Liu, J., An, C.-Y., Zhu, H., Wu, P., Hu, W., Qin, R., Yao, D., et al. (2021) · EMBO Journal · doi:10.15252/embj.2021107739 · Cited by 47
“NKG2D (natural killer group 2, member D) is a potent stimulatory receptor that binds multiple stress-induced ligands to elicit anti-tumor and anti-virus immune responses of both innate and adaptive immune cells (Xu et al , 2011; Raulet et al , 2013; Lanier, 2015).”
Kalathil, S., & Thanavala, Y. (2021) · Cells · doi:10.3390/cells10061332 · Cited by 47
“Nonetheless, viruses and tumor cells devise numerous strategies to evade detection by NKG2D immunosurveillance system [75].”
BackgroundKey Aspects of the Immunobiology of Haploidentical Hematopoietic Cell Transplantation
Baumeister, S., Rambaldi, B., Shapiro, R., & Romee, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00191 · Cited by 47
“NKG2D recognizes MHC-class I related stress-ligands that can be upregulated by tissues in response to infection, inflammation, DNA-damage, and malignant transformation (121), while CD94/NKG2C binds to the non-classical HLAE molecules and senses overall HLA-Class I expression on cells (Figure 5A).”
BackgroundNatural killers join the fight against cancer
Cerwenka, A., & Lanier, L. (2018) · Science · doi:10.1126/science.aat2184 · Cited by 46
Self-citationTan, L., Han, S., Ding, S., Xiao, W.-M., Ding, Y.-B., Qian, L., Wang, C., & Gong, W.-J. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s128032 · Cited by 46
“NKG2D ligands are induced to obtain expression by virus-infected or tumor cells, but they are generally absent in most normal tissues; as such, these ligands serve as tumor-targeted antigens in immunotherapy.(7,8) Chitosan nanoparticles are biodegradable, nontoxic carriers for nucleotides and drugs with potentiality f…”
BackgroundThe Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage
Muter, J., Kong, C., & Brosens, J. J. (2021) · Frontiers in Reproductive Health · doi:10.3389/frph.2021.804921 · Cited by 51
MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma
Zingoni, A., Vulpis, E., Cecere, F., Amendola, M., Fuerst, D., Saribekyan, T., Achour, A., Sandalova, T., Nardone, I., Peri, A., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00926 · Cited by 45
“NKG2D recognizes two families of ligands in humans: the MHC class I chain-related protein A/B (MICA/B) and the UL16-binding proteins (ULBP16) (1).”
BackgroundInfluentialLonez, C., Verma, B. K., Hendlisz, A., Aftimos, P., Awada, A., Neste, E. V. D., Catala, G., Machiels, J., Piette, F., Brayer, J., et al. (2017) · BMJ Open · doi:10.1136/bmjopen-2017-017075 · Cited by 45
NK cells and CD38: Implication for (Immuno)Therapy in Plasma Cell Dyscrasias
Zambello, R., Barilà, G., Manni, S., Piazza, F., & Semenzato, G. (2020) · Cells · doi:10.3390/cells9030768 · Cited by 44
“NKG2D associates with the DAP10 signaling subunit and forms a hexameric complex composed of a single NKG2D homodimer along with two DAP10 homodimers [8].”
BackgroundHuman NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation
Chiesa, M. D., Maria, A. D., Muccio, L., Bozzano, F., Sivori, S., & Moretta, L. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02297 · Cited by 44
“…among which natural cytotoxicity receptors (NCRs) and NKG2D play the Frontiers in Microbiology | www.frontiersin.org 1 October 2019 | Volume 10 | Article 2297 most relevant role in the recognition and killing of infected cells (Bottino et al., 2000; Moretta and Moretta, 2004; Lanier, 2015).”
BackgroundImmune Effects of γδ T Cells in Colorectal Cancer: A Review
Ma, R., Yuan, D., Guo, Y., Yan, R., & Li, K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01600 · Cited by 58
Juengpanich, S., Shi, L., Iranmanesh, Y., Chen, J., Cheng, Z., Khoo, A., Pan, L., Wang, Y.-F., & Cai, X.-J. (2019) · Translational Oncology · doi:10.1016/j.tranon.2019.04.021 · Cited by 43
“73] Lanier LLJCir (2015).”
InfluentialVulpis, E., Soriani, A., Cerboni, C., Santoni, A., & Zingoni, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030611 · Cited by 43
“NKG2D ligands belong to the Retinoic Acid Early Inducible-1 gene, RAE (α−ε), H60 (a–c) and murine UL16-binding protein-like transcript, MULT1 families in mice and to the MHC-related genes, MIC (MICA and MICB) and UL16 binding proteins, ULBP (ULBP1–ULBP6) families in humans [47].”
BackgroundZhang, J., Luo, Q., Li, X., Guo, J., Zhu, Q. K., Lu, X., Wei, L., Xiang, Z., Peng, M., Ou, C., et al. (2023) · Biomarker Research · doi:10.1186/s40364-023-00530-4 · Cited by 41
“NKG2D regulation and lymphocyte stress monitoring are particularly relevant in cancer immunotherapy [3, 6].”
BackgroundTuning the Orchestra: HCMV vs. Innate Immunity
Dell’Oste, V., Biolatti, M., Galitska, G., Griffante, G., Gugliesi, F., Pasquero, S., Zingoni, A., Cerboni, C., & Andrea, M. D. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00661 · Cited by 43
“Another important strategy for immune escape is the ability of HCMV to manipulate the expression of several ligands of the NKG2D receptor, expressed on all NK cells, CD8+ T cells and other T-lymphocyte subsets (e.g., CD4 + T cells, gd, and NKT cells) (Lanier, 2015; Zingoni et al., 2018).”
BackgroundCell-based immunotherapy approaches for multiple myeloma
Kriegsmann, K., Kriegsmann, M., Cremer, M., Schmitt, M. W., Dreger, P., Goldschmidt, H., Müller‐Tidow, C., & Hundemer, M. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0346-9 · Cited by 46
HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion
Enk, J., Levi, A., Weisblum, Y., Yamin, R., Charpak-Amikam, Y., Wolf, D., & Mandelboim, O. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.077 · Cited by 42
Astragaloside III Enhances Anti-Tumor Response of NK Cells by Elevating NKG2D and IFN-γ
Chen, X.-M., Chen, X., Gao, J., Yang, H., Duan, Y., Feng, Y.-X., He, X., Gong, X.-Q., Wang, H.-J., Wu, X.-L., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00898 · Cited by 41
“Clinical investigations have shown that high levels of NKG2D ligands on tumor cells predict favorable prognosis (Lanier, 2015), whereas reduced expression of NKG2D usually correlates with strong prognostic relevance in patients (McGilvray et al., 2009).”
BackgroundOvercoming Target Driven Fratricide for T Cell Therapy
Breman, E., Demoulin, B., Agaugué, S., Mauën, S., Michaux, A., Springuel, L., Houssa, J., Huberty, F., Jacques-Hespel, C., Marchand, C., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02940 · Cited by 42
“As a result, NKG2D ligands are found to be broadly expressed across a majority of hematological and solid tumors (11).”
BackgroundChimeric Antigen Receptors in Different Cell Types: New Vehicles Join the Race
Harrer, D. C., Dörrie, J., & Schaft, N. (2018) · Human Gene Therapy · doi:10.1089/hum.2017.236 · Cited by 41
“55 The upregulation of NK cell inhibitory receptors to avoid NK cell mediated cytotoxicity has also been documented.”
Liu, J., Ye, Z., Mayer, J. G., Hoch, B. A., Green, C., Rolak, L. A., Cold, C. J., Khor, S., Zheng, X., Miyagawa, T., et al. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-103867 · Cited by 38
Advances in CAR-NK cell therapy for hematological malignancies
Yang, R., Yang, Y., Liu, R., Wang, Y., Yang, R., & He, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1414264 · Cited by 38
New cell sources for CAR-based immunotherapy
Mazinani, M., & Rahbarizadeh, F. (2023) · Biomarker Research · doi:10.1186/s40364-023-00482-9 · Cited by 43
CAR T-cells for colorectal cancer immunotherapy: Ready to go?
Ghazi, B., Ghanmi, A. E., Kandoussi, S., Ghouzlani, A., & Badou, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.978195 · Cited by 47
The NKG2D axis: an emerging target in cancer immunotherapy
Lazarova, M., & Steinle, A. (2019) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2019.1580693 · Cited by 40
Serum Interleukin-15 is a Marker of Alopecia Areata Severity
Ebrahim, A., Salem, R., El-fallah, A., & Younis, E. (2019) · International Journal of Trichology · doi:10.4103/ijt.ijt_80_18 · Cited by 40
“Stimulation of this receptor by its ligands has a stimulatory effect on these cells.[4]”
BackgroundSiglec-7 engagement by GBS β-protein suppresses pyroptotic cell death of natural killer cells
Fong, J., Tsai, C.-M., Saha, S., Nizet, V., Varki, A., & Bui, J. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1804108115 · Cited by 40
Liu, M., Hu, Z., Wang, C.-K., & Zhang, Y. (2023) · Journal of molecular medicine · doi:10.1007/s00109-023-02332-5 · Cited by 39
“NKG2D favours tumour resistance and immune evasion by suppressing cytotoxic responses, and its ligand (NKG2DL) can be induced under conditions of cellular stress and malignant transformation [67].”
BackgroundSeliger, B., & Koehl, U. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.910595 · Cited by 42
“Next to CD16 (FcgRIIIA), which interacts with Fc fragments of several IgG subclasses, triggering the ADCC (24), the natural cytotoxicity receptors (NCR) NKp30 (CD337), NKp44 (CD336), NKp46 (CD335), NKp80, DNAM-1 (CD226) and NKG2D (CD314) are the major activating receptors and are able to recognize induced self-ligands…”
BackgroundRole of immunogenetics in the outcome of HCMV infection: implications for ageing
Aiello, A., Accardi, G., Candore, G., Caruso, C., Colomba, C., Di Bona, D., Duro, G., Gambino, C. M., Ligotti, M. E., & Pandey, J. P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030685 · Cited by 38
“but overexpressed in infected or transformed cells [35].”
BackgroundImmune evasion by TGFβ-induced miR-183 repression of MICA/B expression in human lung tumor cells
Trinh, T. L., Kandell, W. M., Donatelli, S. S., Tu, N., Tejera, M. M., Gilvary, D. L., Eksioglu, E. A., Burnette, A., Adams, W. A., Liu, J., et al. (2019) · OncoImmunology · doi:10.1080/2162402x.2018.1557372 · Cited by 43
“Expression of MICA/B can be heterogeneous among tumor types and tumor cell lines.(27,32) In analysis of MICA/B expression in human non-small cell lung carcinoma (NSCLC) cell lines, we found low or absent levels of expression on H1155, H1355, H2170, H1299, A549 and Wi-38.”
BackgroundMekonnen, Y. A., Gültas, M., Effa, K., Hanotte, O., & Schmitt, A. O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01095 · Cited by 37
“…iHS 27 Immune tolerance (Yang et al., 1999; Ganz, 2003) 4920083–4942958 RAETIG Rsb 9 Immune tolerance (Eagle and Trowsdale, 2007; Tomasec et al., 2007; Lanier, 2015) 88232044–88408862 PPP1R14C Rsb 9 Immune tolerance, anemia and neurological dusfunction (Hanke et al., 1996; Linnekin et al., 1997;…”
BackgroundThe role of NK cells in rheumatoid arthritis
Fathollahi, A., Samimi, L. N., Akhlaghi, M., Jamshidi, A., Mahmoudi, M., & Farhadi, E. (2021) · Inflammation Research · doi:10.1007/s00011-021-01504-8 · Cited by 37
NK Cell-Based Immunotherapy in Renal Cell Carcinoma
Terrén, I., Orrantia, A., Mikelez-Alonso, I., Vitallé, J., Zenarruzabeitia, O., & Borrego, F. (2020) · Cancers · doi:10.3390/cancers12020316 · Cited by 40
“On the contrary, they selectively kill target cells that have low levels of MHC class I expression and/or are expressing adequate levels of stress-induced molecules, such as NKG2D ligands, and other ligands for activating receptors [57,62] (Figure 2).”
BackgroundHu, B., Xin, Y., Hu, G., Li, K., & Tan, Y. (2023) · APL Bioengineering · doi:10.1063/5.0156628 · Cited by 36
HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma
Shen, C., Li, M., Duan, Y.-J., Jiang, X., Hou, X.-M., Xue, F., Zhang, Y.-N., & Luo, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1170207 · Cited by 36
Structure-based rational design of a novel chimeric PD1-NKG2D receptor for natural killer cells
Guo, C., Wang, X., Zhang, H., Zhi, L., Lv, T., Li, M., Lu, C., & Zhu, W. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.07.009 · Cited by 40
Espinoza, J. L., & Minami, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00052 · Cited by 45
CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells
Sauer, M., Schuldner, M., Hoffmann, N., Çetintaş, A., Reiners, K., Shatnyeva, O., Hallek, M., Hansen, H., Gasser, S., & von Strandmann, E. P. (2016) · Oncogene · doi:10.1038/onc.2016.259 · Cited by 36
Natural killer cells in cancer immunotherapy
Wang, D., Dou, L., Sui, L., Xue, Y., & Xu, S. (2024) · MedComm · doi:10.1002/mco2.626 · Cited by 47
“12,118 However, there is no MICA/B in mouse cells, and retinoic acid early inducible-1 (Rae-1) family of proteins, H60, and murine ULBP-like transcript 1 (MULT1), which are similar to the MIC protein, serve as NKG2D ligands in mice.”
BackgroundExosomes: Emerging Diagnostic and Therapeutic Targets in Cutaneous Diseases
Khan, A. Q., Akhtar, S., Prabhu, K. S., Zarif, L., Khan, R., Alam, M. A., Buddenkotte, J., Ahmad, A., Steinhoff, M. S., & Shahab Uddin, M. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239264 · Cited by 43
Tumor-Derived Soluble MICA Obstructs the NKG2D Pathway to Restrain NK Cytotoxicity
Luo, Q., Luo, W., Zhu, Q., Huang, H.-J., Peng, H.-Z., Liu, R., Xie, M., Li, S.-L., Li, M., Hu, X., et al. (2020) · Aging and Disease · doi:10.14336/ad.2019.1017 · Cited by 35
“The reduction of NK cellmediate killing during viral infection and tumor genesis is associated with a decrease in levels of the NKG2D receptor and NKG2D receptor ligands [12].”
BackgroundVyas, M., Reinartz, S., Hoffmann, N., Reiners, K., Lieber, S., Jansen, J. M., Wagner, U., Müller, R., & von Strandmann, E. P. (2017) · Oncoimmunology · doi:10.1080/2162402x.2017.1339854 · Cited by 35
“Engagement of NKG2D on NK cells results in direct target cell killing and release of pro-inflammatory cytokines, while NKG2D expressed on the subsets of T cells provides costimulation.(21,28,42)”
BackgroundHarnessing Natural Killer Cells in Non-Small Cell Lung Cancer
Russell, É., Conroy, M. J., & Barr, M. P. (2022) · Cells · doi:10.3390/cells11040605 · Cited by 37
“NKG2D ligands are normally absent or expressed at low levels on healthy cells but become upregulated on tumor cells, allowing for detection by immune cells [80].”
BackgroundZhao, R., Cheng, L., Jiang, Z.-W., Wei, X.-R., Li, B.-H., Wu, Q., Wang, S., Lin, S.-M., Long, Y., Zhang, X.-C., et al. (2018) · Oncoimmunology · doi:10.1080/2162402x.2018.1509173 · Cited by 34
More than Decoration: Roles for Natural Killer Group 2 Member D Ligand Expression by Immune Cells
Trembath, A. P., & Markiewicz, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00231 · Cited by 34
Dassa, L., Seidel, E., Oiknine-Djian, E., Yamin, R., Wolf, D., Le-Trilling, V., & Mandelboim, O. (2018) · Journal of Virology · doi:10.1128/jvi.00162-18 · Cited by 33
“One key activating receptor expressed by NK cells is NKG2D (11, 12).”
BackgroundThe Role of Natural Killer Group 2, Member D in Chronic Inflammation and Autoimmunity
Babić, M., & Romagnani, C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01219 · Cited by 33
“Gastroenterology (2011) 141(1):217–26, 226.”
BackgroundInfluentialHongo, D., Tang, X., Zhang, X.-Y., Engleman, E., & Strober, S. (2017) · Blood · doi:10.1182/blood-2016-07-723015 · Cited by 33
Chimienti, R., Baccega, T., Torchio, S., Manenti, F., Pellegrini, S., Cospito, A., Amabile, A., Lombardo, M. T., Monti, P., Sordi, V., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111423 · Cited by 32
“Specifically, NKG2D-mediated cytotoxicity against stem cells was explained by the expression of MICA, and such response could be likely involved in the outcome of transplantation of the iPSC derivatives.”
BackgroundInfluentialEngineering γδ T Cells: Recognizing and Activating on Their Own Way
Dong, R., Zhang, Y., Xiao, H., & Zeng, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.889051 · Cited by 37
“These ligands can be induced in infected and oncogenic transformed cells (85, 86).”
BackgroundNK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells
Babić, M., Dimitropoulos, C., Hammer, Q., Stehle, C., Heinrich, F., Sarsenbayeva, A., Eisele, A. S., Durek, P., Mashreghi, M., Lisnić, B., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190133 · Cited by 35
“Based on this, NKG2D expressed by NK, CD8+, and γδ+ T cells plays an important role in the recognition and clearance of infected and transformed cells expressing cognate ligands (Jonjić et al., 2008; Lanier, 2015; Strid et al., 2011).”
BackgroundDamage-Associated Molecular Patterns in Human Diseases
Land, W. (2018) · Cambridge International Law Journal · doi:10.1007/978-3-319-78655-1 · Cited by 32
“On the other hand—as splendidly outlined by Lanier [264]—where DAMP-activated NKG2D-bearing cells contribute to aggravate autoimmune responses, suppression of expression of these DAMPs in inflammation provides an attractive therapeutic target.”
BackgroundHosomi, S., Grootjans, J., Huang, Y., Kaser, A., & Blumberg, R. S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01324 · Cited by 35
“Interaction of these ligands with NKG2D results in NK cell cytotoxicity via signal transducing adapter molecule DAP10 in human and both DAP10 and DAP12 in mouse (10).”
BackgroundNakajima, N. I., Niimi, A., Isono, M., Oike, T., Sato, H., Nakano, T., & Shibata, A. (2017) · Oncology Reports · doi:10.3892/or.2017.5773 · Cited by 32
“Major histocompatibility complex class I-related chains A and B (MICA/B), ligands for the NKG2D immune receptor, in human cells are often constitutively upregulated in cancer cells, but are not effectively recognized in an immunosuppressive environment (6).”
BackgroundMa, Y., Gong, J.-Y., Liu, Y., Guo, W.-W., Jin, B.-Q., Wang, X.-H., & Chen, L.-H. (2016) · Life Science · doi:10.1016/j.lfs.2016.03.012 · Cited by 32
Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review
Lyu, D. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2023.1292580 · Cited by 31
“Cytotoxicity receptor NKG2D uses MICA and MICB as ligands and destroys cancer cells (Lanier, 2015).”
BackgroundValproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia
Wen, J., Chen, Y., Yang, J., Dai, C., Yu, S., Zhong, W., Liu, L., He, C., Zhang, W., Yang, T., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-006857 · Cited by 34
Franzese, O., & Graziani, G. (2022) · Cancers · doi:10.3390/cancers14225633 · Cited by 44
SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D
Lee, M. J., Leong, M. W., Rustagi, A., Beck, A., Zeng, L., Holmes, S., Qi, L., & Blish, C. (2022) · bioRxiv · doi:10.1016/j.celrep.2022.111892 · Cited by 31
Oliviero, B., Varchetta, S., Mele, D., Pessino, G., Maiello, R., Falleni, M., Tosi, D., Donadon, M., Soldani, C., Franceschini, B., et al. (2022) · Oncoimmunology · doi:10.1080/2162402x.2022.2035919 · Cited by 31
“NK-mediated target cell lysis occurs through reduced expression of inhibitory signals and a simultaneously increased expression of activating signals required for NK cell triggering.(16) In humans, NKG2D ligands (NKG2DL) include major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA), MHC…”
BackgroundAnti-NKG2D single domain-based antibodies for the modulation of anti-tumor immune response
Raynaud, A., Even-Desrumeaux, K., Vidard, L., Termine, E., Baty, D., Chames, P., Vigne, E., & Kerfélec, B. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1854529 · Cited by 44
“Seven ISVDs, representative of three clusters (AR3, 6, and 11) or unique (AR18, 19, 20, and 23), were selected for the construction of bivalent monospecific and monovalent bispecific antibodies 47,48 for in-depth characterization.”
InfluentialJin, W. J., Erbe, A. K., Schwarz, C. N., Jaquish, A. A., Anderson, B. R., Sriramaneni, R. N., Jagodinsky, J. C., Bates, A. M., Clark, P. A., Le, T. Q. H., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.591139 · Cited by 41
“Many tumors express NKG2D ligands and these are upregulated by cell stress and enhance the susceptibility of cells to elimination by cytotoxic NK cells (50, 51).”
BackgroundHitting More Birds with a Stone: Impact of TGF-β on ILC Activity in Cancer
Fionda, C., Stabile, H., Cerboni, C., Soriani, A., Gismondi, A., Cippitelli, M., & Santoni, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9010143 · Cited by 31
“This group of receptors includes the natural cytotoxicity receptors (NCRs: NKp30, NKp44, NKp46) [12,13], the C-type lectin-like receptors (NKG2D (natural-killer group 2, member D) and CD94/NKG2C) [14], the activating forms of KIR, the adhesion molecule and co-activating receptor DNAM-1(DNAX accessory molecule-1) [15],…”
BackgroundXie, H.-T., Zhang, Q., Zhou, H., Zhou, J., Zhang, J., Jiang, Y., Wang, J.-H., Meng, X.-D., Zeng, L.-P., & Jiang, X.-X. (2018) · Cytotechnology (Dordrecht) · doi:10.1007/s10616-017-0108-1 · Cited by 31
Michaux, A., Mauën, S., Breman, E., Dheur, M.-S., Twyffels, L., Saerens, L., Jacques-Hespel, C., Gauthy, E., Agaugué, S., Gilham, D., et al. (2022) · Journal of immunotherapy · doi:10.1097/cji.0000000000000413 · Cited by 30
Tong, D. L., Kempsell, K. E., Szakmány, T., & Ball, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00380 · Cited by 30
Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer
Cheng, M., Zhu, W.-P., Li, Q., Dai, D.-J., & Hou, Y. (2017) · OncoTarget · doi:10.18632/oncotarget.19146 · Cited by 30
“The expression of Rae-1 is induced by NKG2D and is mediated by the DAP10 pathway (the “selfinduction hypothesis”) [5].”
BackgroundYao, Y., Strauss-Albee, D. M., Zhou, J. Q., Malawista, A., Garcia, M. N., Murray, K., Blish, C., & Montgomery, R. R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172625 · Cited by 30
The metabolism of cells regulates their sensitivity to NK cells depending on p53 status
Belkahla, S., Marco-Brualla, J., de Maudave, A. F., Falvo, P., Allende-Vega, N., Constantinides, M., Khan, A. U. H., Coënon, L., Alexia, C., Mitola, G., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-07281-6 · Cited by 35
Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma
Wang, J., Li, C.-D., & Sun, L. (2020) · Biomolecules · doi:10.3390/biom10020301 · Cited by 28
“cells (iNKT) [38] Usually express Usually express”
Anti-NKG2D mAb: A New Treatment for Crohn’s Disease?
Vadstrup, K., & Bendtsen, F. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091997 · Cited by 28
“NKG2D is an activating receptor expressed on human NK, γδ T, mucosal-associated invariant T (MAIT), CD56+ T, and CD8+ T cells [8,15], which can participate in the recognition of inducible “stressed-self” ligands on the surface of target cells.”
BackgroundRewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics
Lyu, S., Gildor, N., Zhang, Q. H., & Liao, C. (2025) · Science China Life Sciences · doi:10.1007/s11427-025-2979-3 · Cited by 27
“Elevated purine nucleotide levels can induce the expression of MHC class I polypeptide-related sequence A (MICA), enhancing immune recognition and the elimination of cancerous or virus-infected cells (Lanier, 2015; McCarthy et al., 2018).”
State of the Art in CAR-T Cell Therapy for Solid Tumors: Is There a Sweeter Future?
Amorós-Pérez, B., Rivas-Pardo, B., del Moral, M. G., Subiza, J. L., & Martı́nez-Naves, E. (2024) · Cells · doi:10.3390/cells13090725 · Cited by 34
“Recognition of NKG2DLs on the surface of stressed cells by the immune system leads to the elimination of the targeted cell [68].”
BackgroundChen, Y., Zhu, Y., Kramer, A. B., Fang, Y., Wilson, M., Li, Y.-R., & Yang, L. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1135468 · Cited by 26
“, DNAM-1, NKG2D, NKp33) permit alternative, TCR-independent recognition of tumors (129, 130).”
BackgroundGoulding, J., Yeh, W.-I., Hancock, B., Blum, R., Xu, T., Yang, B.-H., Chang, C., Groff, B. C., Avramis, E. V., Pribadi, M., et al. (2023) · Med · doi:10.1016/j.medj.2023.04.004 · Cited by 28
The Glycosylation of Immune Checkpoints and Their Applications in Oncology
Zheng, L., Yang, Q., Li, F., Zhu, M., Yang, H., Tan, T., Wu, B., Liu, M.-X., Xu, C., Yin, J., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15121451 · Cited by 26
Escape of tumor cells from the NK cell cytotoxic activity
Cantoni, C., Wurzer, H., Thomas, C., & Vitale, M. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.2mr0820-652r · Cited by 38
Molfetta, R., Zingoni, A., Santoni, A., & Paolini, R. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02557 · Cited by 26
“Human NKG2D ligands (NKG2DLs) belong to two families of polymorphic molecules structurally related to MHC class I: the MHC class I related proteins (MIC)A/B which possess α1, α2, and α3 domains similar to MHC molecules and six UL16 binding proteins (ULBP1-6) characterized by α1 and α2 domains (15, 18, 19).”
BackgroundCelyad's novel CAR T-cell therapy for solid malignancies.
Lonez, C., Hendlisz, A., Shaza, L., Aftimos, P., Vouche, M., Donckier, V., Machiels, J., den Eynde, M. V., Canon, J., Carrasco, J., et al. (2018) · Current Research in Translational Medicine · doi:10.1016/j.retram.2018.03.001 · Cited by 26
“NKG2D is an innate immune activating receptor expressed in humans mainly by natural killer (NK) cells but also by activated CD8 T-cells, NK Tcells, and some CD4 and gd T-cell subsets [10] and whose function is to recognize and kill infected or cancer cells.”
BackgroundNabekura, T., Gotthardt, D., Niizuma, K., Trsan, T., Jenus, T., Jonjić, S., & Lanier, L. (2017) · Journal of Immunology · doi:10.4049/jimmunol.1700799 · Cited by 26
“Because NKG2D ligands are express by many tumors and by cells infected with numerous pathogens (37), if NKG2D receptor signaling were capable of driving NK cell expansion, this would be beneficial in host defense and provide a therapeutic opportunity for cancer.”
BackgroundSelf-citationAdvances in natural killer cell therapies for breast cancer
Kiaei, S. Z. F., Nouralishahi, A., Ghasemirad, M., Barkhordar, M., Ghaffari, S., Kheradjoo, H., Saleh, M., Mohammadzadehsaliani, S., & Molaeipour, Z. (2023) · Immunology and Cell Biology · doi:10.1111/imcb.12658 · Cited by 30
“MHC-I homologs MICA/B and ULBP (cytomegalovirus UL16-binding protein) are two examples of NKG2D ligands in humans.(50) In response to the recognition of these ligands, NKG2D receptors are activated by the adapter protein DNAX-activating protein 10 (DAP10).”
BackgroundHirano, M., Imai, Y., Kaito, Y., Murayama, T., Sato, K., Ishida, T., Yamamoto, J., Ito, T., Futami, M., Ri, M., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01909-7 · Cited by 25
Checkpoint-modulating immunotherapies in tumor treatment: Targets, drugs, and mechanisms
Sun, L., Chen, L., & Li, H. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.12.006 · Cited by 34
Immunosurveillance by human γδ T lymphocytes: the emerging role of butyrophilins
Kabelitz, D., Lettau, M., & Janßen, O. (2017) · F1000Research · doi:10.12688/f1000research.11057.1 · Cited by 24
“In addition to the TCR, γδ T cells express other activating cell surface receptors, notably natural killer group 2 member D (NKG2D), which is a receptor for multiple stress-inducible MHC class I-related molecules including MICA/B and six members of the UL16 binding protein family (ULBP1-6) 32 .”
BackgroundNKG2D-bispecific enhances NK and CD8+ T cell antitumor immunity
Hérault, A., Mak, J., Cruz-Chuh, J. D., Dillon, M., Ellerman, D. A., Go, M., Cosino, E., Clark, R., Carson, E., Yeung, S., et al. (2024) · Cancer Immunology and Immunotherapy · doi:10.1007/s00262-024-03795-2 · Cited by 24
“While NKG2D agonism can lead to NK cell activation or co-stimulation depending on species, NKG2D acts as a co-stimulatory receptor for T cells [14–16].”
BackgroundZhang, Y.-P., Liang, K.-J., Zhou, X., Zhang, X., Xu, H., Dai, H., Song, X., Yang, X., Liu, B.-R., Shi, T., et al. (2023) · Cancer Science · doi:10.1111/cas.15828 · Cited by 24
Wang, J., Dai, Z., Miao, Y., Zhao, T., Gan, J., Zhao, C., Ran, J., & Guan, Q. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.09.003 · Cited by 26
Role of Natural Killer Cells in Uveal Melanoma
Javed, A., & Milhem, M. M. (2020) · Cancers · doi:10.3390/cancers12123694 · Cited by 25
“In humans, ligands for NKG2D include the non-classical MHC molecules MIC-A, MIC-B and the UL16-binding proteins, ULBP1–4 [144,145].”
BackgroundZhu, M., Li, M., Zhou, W., Yang, Y., Li, F., Zhang, L. R., & Ji, G. (2019) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-019-2577-6 · Cited by 24
“Klrk1, also known as Nkg2d, is an activating receptor expressed on the surface of NK cells, CD8 T cells, and subsets of CD4T cells and invariant NKT cells [49].”
BackgroundImpact of bone marrow-derived signals on NK cell development and functional maturation.
Stabile, H., Fionda, C., Santoni, A., & Gismondi, A. (2018) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2018.03.008 · Cited by 24
Metadata
- Authors
- Lanier, L. L.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Lanier, Lewis L.
- ORCID
- Lanier, Lewis L.
- Venue
- Cancer Immunology Research
- Published
- 2015-06-01
- Volume
- 3
- Issue
- 6
- Pages
- 575-582
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- PMC
- PMC4457299
- OpenAlex
- W2142548447
- Cited by
- 599
- References
- 78
- Citations by year
- 2026: 27 · 2025: 53 · 2024: 56 · 2023: 73 · 2022: 56 · 2021: 66 · 2020: 63 · 2019: 51 · 2018: 65 · 2017: 47 · 2016: 37 · 2015: 4
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Immunology Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R01CA089189)
- National Institute of Allergy and Infectious Diseases (AI-068129, R01AI068129, R37AI066897, AI066897)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- NKG2D, NKG2D ligands, mica, MICB, natural killer cells, DAP10, DAP12, immune evasion, viral evasion, tumor immune evasion, host defense, NK cell activation
- MeSH terms
- Animals, Communicable Diseases, Humans, Killer Cells, Natural, Ligands, Lymphocyte Activation, Neoplasms, Lymphocyte Subsets, NK Cell Lectin-Like Receptor Subfamily K, Disease Resistance
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