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PERSPECTIVE ARTICLE

Combination cancer therapy integrating T-cell immune checkpoint blockers and natural killer cell activation

Junyi Li1 ,  Yanzhang Wei1*
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1 Department of Biological Sciences, College of Science, Clemson University, Clemson, South Carolina, United States of America
GPD, 3804 https://doi.org/10.36922/gpd.3804
Submitted: 31 May 2024 | Accepted: 29 August 2024 | Published: 4 October 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

T-cell immune checkpoint blockers (ICBs) and natural killer (NK) cell activation have emerged as promising strategies for cancer therapy in recent years. In this approach, ICBs target inhibitory receptors on cytotoxic immune cells, such as programmed death Protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), to enhance immune cell cytotoxicity against cancer cells in a CD8+ T cell-dependent manner. Meanwhile, NK cells play a critical role in immunosurveillance through their direct cytotoxic effects, which do not require prior activation. NK cell activation is mediated by receptors such as NK Group 2 member D (NKG2D), which regulates NK cell function and cytotoxicity through the upregulation of cytokine production. Individually, these treatments target only a limited subset of cancer patients and often face great resistance rates after treatment. However, combining ICBs with NK cell activation may produce a synergistic therapeutic effect, potentially improving treatment outcomes. This perspective article discusses the mechanisms of action of T cell-related PD-1/PDL1 pathways and NK cell activation through NKG2D, examining current studies that provide a rationale for combined NK/T cell combination therapy. The potential of this dual-combination approach to enhance anti-tumor immunity is highlighted. Future perspectives suggest the potential development of chimeric antibodies targeting both T cells and NK cells as a novel therapeutic strategy for cancer treatment.

Keywords
Immune checkpoint blockers
PD-1/PD-L1
Natural killer cell activation
NKG2D
Funding
None.
Conflict of interest
The authors declare no conflict of interest to any group.
References
  1. Smith SM, Wachter K, Burris HA 3rd, et al. Clinical cancer advances 2021: ASCO’s report on progress against cancer. J Clin Oncol. 2021;39(10):1165-1184. doi: 10.1200/jco.20.03420

 

  1. Sadeghi Rad H, Monkman J, Warkiani ME, et al. Understanding the tumor microenvironment for effective immunotherapy. Med Res Rev. 2021;41(3):1474-1498. doi: 10.1002/med.21765

 

  1. Thorsson V, Gibbs DL, Brown SD, et al. The immune landscape of cancer. Immunity. 2018;48(4):812-830.e14. doi: 10.1016/j.immuni.2018.03.023

 

  1. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450-461. doi: 10.1016/j.ccell.2015.03.001

 

  1. Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and anti- CTLA-4 therapies in cancer: Mechanisms of action, efficacy, and limitations. Front Oncol. 2018;8:86. doi: 10.3389/fonc.2018.00086

 

  1. André P, Denis C, Soulas C, et al. Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell. 2018;175(7):1731-1743.e13. doi: 10.1016/j.cell.2018.10.014

 

  1. Carotta S. Targeting NK cells for anticancer immunotherapy: Clinical and preclinical approaches. Front Immunol. 2016;7:152. doi: 10.3389/fimmu.2016.00152

 

  1. Sivori S, Vacca P, Del Zotto G, Munari E, Mingari MC, Moretta L. Human NK cells: Surface receptors, inhibitory checkpoints, and translational applications. Cell Mol Immunol. 2019;16(5):430-441. doi: 10.1038/s41423-019-0206-4

 

  1. Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH. Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol. 2016;34:539-573. doi: 10.1146/annurev-immunol-032414-112049

 

  1. Rolfo C, Caglevic C, Santarpia M, et al. Immunotherapy in NSCLC: A promising and revolutionary weapon. Adv Exp Med Biol. 2017;995:97-125. doi: 10.1007/978-3-319-53156-4_5

 

  1. Li JX, Huang JM, Jiang ZB, et al. Current clinical progress of PD-1/PD-L1 immunotherapy and potential combination treatment in non-small cell lung cancer. Integr Cancer Ther. 2019;18:1534735419890020. doi: 10.1177/1534735419890020

 

  1. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341-351. doi: 10.1056/NEJMoa1805131

 

  1. Shirley M. Avelumab: A review in metastatic merkel cell carcinoma. Target Oncol. 2018;13(3):409-416. doi: 10.1007/s11523-018-0571-4

 

  1. Paz-Ares L, Spira A, Raben D, et al. Outcomes with durvalumab by tumour PD-L1 expression in unresectable, stage III non-small-cell lung cancer in the PACIFIC trial. Ann Oncol. 2020;31(6):798-806. doi: 10.1016/j.annonc.2020.03.287

 

  1. Liebl MC, Hofmann TG. Identification of responders to immune checkpoint therapy: Which biomarkers have the highest value? J Eur Acad Dermatol Venereol. 2019;33 Suppl 8:52-56. doi: 10.1111/jdv.15992

 

  1. Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer. 2017;8(3):410-416. doi: 10.7150/jca.17144

 

  1. Sinner F, Pinter M, Scheiner B, et al. Atezolizumab plus bevacizumab in patients with advanced and progressing hepatocellular carcinoma: Retrospective multicenter experience. Cancers (Basel). 2022;14(23):5966. doi: 10.3390/cancers14235966

 

  1. du Rusquec P, de Calbiac O, Robert M, Campone M, Frenel JS. Clinical utility of pembrolizumab in the management of advanced solid tumors: An evidence-based review on the emerging new data. Cancer Manag Res. 2019;11:4297-4312. doi: 10.2147/cmar.s151023

 

  1. Kim N, Kim HS. Targeting checkpoint receptors and molecules for therapeutic modulation of natural killer cells. Front Immunol. 2018;9:2041. doi: 10.3389/fimmu.2018.02041

 

  1. O’Sullivan TE, Sun JC, Lanier LL. Natural killer cell memory. Immunity. 2015;43(4):634-645. doi: 10.1016/j.immuni.2015.09.013

 

  1. Cao Y, Wang X, Jin T, et al. Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy. Signal Transduct Target Ther. 2020;5(1):250. doi: 10.1038/s41392-020-00348-8

 

  1. Thielens A, Vivier E, Romagné F. NK cell MHC class I specific receptors (KIR): from biology to clinical intervention. Curr Opin Immunol. 2012;24(2):239-245. doi: 10.1016/j.coi.2012.01.001

 

  1. Pende D, Falco M, Vitale M, et al. Killer Ig-like receptors (KIRs): Their role in NK cell modulation and developments leading to their clinical exploitation. Front Immunol. 2019;10:1179. doi: 10.3389/fimmu.2019.01179

 

  1. Sun H, Sun C. The rise of NK cell checkpoints as promising therapeutic targets in cancer immunotherapy. Front Immunol. 2019;10:2354. doi: 10.3389/fimmu.2019.02354

 

  1. McWilliams EM, Mele JM, Cheney C, et al. Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia. Oncoimmunology. 2016;5(10):e1226720. doi: 10.1080/2162402x.2016.1226720

 

  1. Seo H, Kim BS, Bae EA, et al. IL21 therapy combined with PD-1 and Tim-3 blockade provides enhanced NK cell antitumor activity against MHC class I-deficient tumors. Cancer Immunol Res. 2018;6(6):685-695. doi: 10.1158/2326-6066.cir-17-0708

 

  1. Seo H, Jeon I, Kim BS, et al. IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours. Nat Commun. 2017;8:15776. doi: 10.1038/ncomms15776

 

  1. Deng W, Gowen BG, Zhang L, et al. Antitumor immunity. A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection. Science. 2015;348(6230):136-139. doi: 10.1126/science.1258867

 

  1. Luo Q, Luo W, Zhu Q, et al. Tumor-derived soluble MICA obstructs the NKG2D pathway to restrain NK cytotoxicity. Aging Dis. 2020;11(1):118-128. doi: 10.14336/ad.2019.1017

 

  1. Ames E, Canter RJ, Grossenbacher SK, et al. NK cells preferentially target tumor cells with a cancer stem cell phenotype. J Immunol. 2015;195(8):4010-4019. doi: 10.4049/jimmunol.1500447

 

  1. Cai X, Zhan H, Ye Y, et al. Current progress and future perspectives of immune checkpoint in cancer and infectious diseases. Front Genet. 2021;12:785153. doi: 10.3389/fgene.2021.785153

 

  1. Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: Long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19(4):254-267. doi: 10.1038/s41571-022-00600-w

 

  1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. doi: 10.1038/nrc3239

 

  1. Melero I, Rouzaut A, Motz GT, Coukos G. T-cell and NK-cell infiltration into solid tumors: A key limiting factor for efficacious cancer immunotherapy. Cancer Discov. 2014;4(5):522-526. doi: 10.1158/2159-8290.cd-13-0985

 

  1. Melaiu O, Lucarini V, Cifaldi L, Fruci D. Influence of the tumor microenvironment on NK cell function in solid tumors. Front Immunol. 2019;10:3038. doi: 10.3389/fimmu.2019.03038

 

  1. Blank CU, Haining WN, Held W, et al. Defining “T cell exhaustion”. Nat Rev Immunol. 2019;19(11):665-674. doi: 10.1038/s41577-019-0221-9

 

  1. Philip M, Fairchild L, Sun L, et al. Chromatin states define tumour-specific T cell dysfunction and reprogramming. Nature. 2017;545(7655):452-456. doi: 10.1038/nature22367

 

  1. Shim YJ, Khedraki R, Dhar J, et al. Early T cell infiltration is modulated by programed cell death-1 protein and its ligand (PD-1/PD-L1) interactions in murine kidney transplants. Kidney Int. 2020;98(4):897-905. doi: 10.1016/j.kint.2020.03.037

 

  1. Habif G, Crinier A, André P, Vivier E, Narni-Mancinelli E. Targeting natural killer cells in solid tumors. Cell Mol Immunol. 2019;16(5):415-422. doi: 10.1038/s41423-019-0224-2

 

  1. Huang Q, Huang M, Meng F, Sun R. Activated pancreatic stellate cells inhibit NK cell function in the human pancreatic cancer microenvironment. Cell Mol Immunol. 2019;1:87-89. doi: 10.1038/s41423-018-0014-2

 

  1. Castriconi R, Dondero A, Bellora F, et al. Neuroblastoma-derived TGF-β1 modulates the chemokine receptor repertoire of human resting NK cells. J Immunol. 2013;190(10):5321-5328. doi: 10.4049/jimmunol.1202693

 

  1. Yoon SR, Kim TD, Choi I. Understanding of molecular mechanisms in natural killer cell therapy. Exp Mol Med. 2015;47(2):e141. doi: 10.1038/emm.2014.114

 

  1. Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020;11(1):3801. doi: 10.1038/s41467-020-17670-y

 

  1. Riella LV, Paterson AM, Sharpe AH, Chandraker A. Role of the PD-1 pathway in the immune response. Am J Transplant. 2012;12(10):2575-2587. doi: 10.1111/j.1600-6143.2012.04224.x

 

  1. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. Embo J. 1992;11(11):3887-3895. doi: 10.1002/j.1460-2075.1992.tb05481.x

 

  1. Neel BG, Gu H, Pao L. The “Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci. 2003;28(6):284-293. doi: 10.1016/s0968-0004(03)00091-4

 

  1. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: Current researches in cancer. Am J Cancer Res. 2020;10(3):727-742.

 

  1. Ahmadzadeh M, Johnson LA, Heemskerk B, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114(8):1537-1544. doi: 10.1182/blood-2008-12-195792

 

  1. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. doi: 10.1146/annurev.immunol.26.021607.090331

 

  1. Staron MM, Gray SM, Marshall HD, et al. The transcription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8(+) T cells during chronic infection. Immunity. 2014;41(5):802-814. doi: 10.1016/j.immuni.2014.10.013

 

  1. Morimoto Y, Kishida T, Kotani SI, Takayama K, Mazda O. Interferon-β signal may up-regulate PD-L1 expression through IRF9-dependent and independent pathways in lung cancer cells. Biochem Biophys Res Commun. 2018;507(1-4):330-336. doi: 10.1016/j.bbrc.2018.11.035

 

  1. Mathieu M, Cotta-Grand N, Daudelin JF, Thébault P, Labrecque N. Notch signaling regulates PD-1 expression during CD8(+) T-cell activation. Immunol Cell Biol. 2013;91(1):82-88. doi: 10.1038/icb.2012.53

 

  1. Kinter AL, Godbout EJ, McNally JP, et al. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J Immunol. 2008;181(10):6738-6746. doi: 10.4049/jimmunol.181.10.6738

 

  1. Oestreich KJ, Yoon H, Ahmed R, Boss JM. NFATc1 regulates PD-1 expression upon T cell activation. J Immunol. 2008;181(7):4832-4839. doi: 10.4049/jimmunol.181.7.4832

 

  1. Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8(3):239-245. doi: 10.1038/ni1443

 

  1. Yamazaki T, Akiba H, Iwai H, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002;169(10):5538-5545. doi: 10.4049/jimmunol.169.10.5538

 

  1. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027-1034. doi: 10.1084/jem.192.7.1027

 

  1. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5(12):1365-1369. doi: 10.1038/70932

 

  1. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800. doi: 10.1038/nm730

 

  1. Trabattoni D, Saresella M, Biasin M, et al. B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression. Blood. 2003;101(7):2514-2520. doi: 10.1182/blood-2002-10-3065

 

  1. Zheng Y, Fang YC, Li J. PD-L1 expression levels on tumor cells affect their immunosuppressive activity. Oncol Lett. 2019;18(5):5399-5407. doi: 10.3892/ol.2019.10903

 

  1. Latchman YE, Liang SC, Wu Y, et al. PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci U S A. 2004;101(29):10691-10696. doi: 10.1073/pnas.0307252101

 

  1. Torphy RJ, Schulick RD, Zhu Y. Newly emerging immune checkpoints: Promises for future cancer therapy. Int J Mol Sci. 2017;18(12):2642. doi: 10.3390/ijms18122642

 

  1. Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004;173(2):945-954. doi: 10.4049/jimmunol.173.2.945

 

  1. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543-9553. doi: 10.1128/mcb.25.21.9543-9553.2005

 

  1. Carter L, Fouser LA, Jussif J, et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol. 2002;32(3):634-643. doi: 10.1002/1521-4141(200203)32:3<634::aid-immu634>3.0.co;2-9

 

  1. Ding G, Shen T, Yan C, Zhang M, Wu Z, Cao L. IFN-γ down-regulates the PD-1 expression and assist nivolumab in PD-1-blockade effect on CD8+ T-lymphocytes in pancreatic cancer. BMC Cancer. 2019;19(1):1053. doi: 10.1186/s12885-019-6145-8

 

  1. Lai X, Hao W, Friedman A. TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model. PLoS One. 2020;15(4):e0231499. doi: 10.1371/journal.pone.0231499

 

  1. Keir ME, Liang SC, Guleria I, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203(4):883-895. doi: 10.1084/jem.20051776

 

  1. Darvin P, Sasidharan Nair V, Elkord E. PD-L1 expression in human breast cancer stem cells is epigenetically regulated through posttranslational histone modifications. J Oncol. 2019;2019:3958908. doi: 10.1155/2019/3958908

 

  1. Takada K, Toyokawa G, Okamoto T, et al. A comprehensive analysis of programmed cell death ligand-1 expression with the clone SP142 antibody in non-small-cell lung cancer patients. Clin Lung Cancer. 2017;18(5):572-582.e1. doi: 10.1016/j.cllc.2017.02.004

 

  1. Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother. 2007;56(8):1173-1182. doi: 10.1007/s00262-006-0266-z

 

  1. Schiwitza A, Schildhaus HU, Zwerger B, et al. Monitoring efficacy of checkpoint inhibitor therapy in patients with non-small-cell lung cancer. Immunotherapy. 2019;11(9):769-782. doi: 10.2217/imt-2019-0039

 

  1. Mager L, Gardeen S, Carr DR, Shahwan KT. Cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma: Appropriate patient selection and perspectives. Clin Cosmet Investig Dermatol. 2023;16:2135-2142. doi: 10.2147/ccid.s381471

 

  1. Lantuejoul S, Damotte D, Hofman V, Adam J. Programmed death ligand 1 immunohistochemistry in non-small cell lung carcinoma. J Thorac Dis. 2019;11(Suppl 1):S89-S101. doi: 10.21037/jtd.2018.12.103

 

  1. Atkins MB, Tannir NM. Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treat Rev. 2018;70:127-137. doi: 10.1016/j.ctrv.2018.07.009

 

  1. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 2020;383(14):1328-1339. doi: 10.1056/NEJMoa1917346

 

  1. Morvan MG, Lanier LL. NK cells and cancer: You can teach innate cells new tricks. Nat Rev Cancer. 2016;16(1):7-19. doi: 10.1038/nrc.2015.5

 

  1. Sun JC, Lanier LL. NK cell development, homeostasis and function: Parallels with CD8⁺ T cells. Nat Rev Immunol. 2011;11(10):645-657. doi: 10.1038/nri3044

 

  1. Yu J, Freud AG, Caligiuri MA. Location and cellular stages of natural killer cell development. Trends Immunol. 2013;34(12):573-582. doi: 10.1016/j.it.2013.07.005

 

  1. Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: Function, dysfunction and human pathology. Nat Rev Immunol. 2015;15(6):388-400. doi: 10.1038/nri3839

 

  1. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503-510. doi: 10.1038/ni1582

 

  1. Houchins JP, Yabe T, McSherry C, Bach FH. DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J Exp Med. 1991;173(4):1017-1020. doi: 10.1084/jem.173.4.1017

 

  1. Yabe T, McSherry C, Bach FH, et al. A multigene family on human chromosome 12 encodes natural killer-cell lectins. Immunogenetics. 1993;37(6):455-460. doi: 10.1007/bf00222470

 

  1. Diefenbach A, Tomasello E, Lucas M, et al. Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol. 2002;3(12):1142-1149. doi: 10.1038/ni858

 

  1. Wu J, Song Y, Bakker AB, et al. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999;285(5428):730-732. doi: 10.1126/science.285.5428.730

 

  1. Upshaw JL, Arneson LN, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ. NKG2D-mediated signaling requires a DAP10- bound Grb2-Vav1 intermediate and phosphatidylinositol- 3-kinase in human natural killer cells. Nat Immunol. 2006;7(5):524-532. doi: 10.1038/ni1325

 

  1. Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 1998;391(6668):703-707. doi: 10.1038/35642

 

  1. Duan S, Guo W, Xu Z, et al. Natural killer group 2D receptor and its ligands in cancer immune escape. Mol Cancer. 2019;18(1):29. doi: 10.1186/s12943-019-0956-8

 

  1. Zompi S, Hamerman JA, Ogasawara K, et al. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol. 2003;4(6):565-572. doi: 10.1038/ni930

 

  1. Bahram S, Bresnahan M, Geraghty DE, Spies T. A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1994;91(14):6259-6263. doi: 10.1073/pnas.91.14.6259

 

  1. Zhang J, Basher F, Wu JD. NKG2D ligands in tumor immunity: Two sides of a coin. Front Immunol. 2015;6:97. doi: 10.3389/fimmu.2015.00097

 

  1. González S, López-Soto A, Suarez-Alvarez B, López- Vázquez A, López-Larrea C. NKG2D ligands: Key targets of the immune response. Trends Immunol. 2008;29(8):397-403. doi: 10.1016/j.it.2008.04.007

 

  1. Zhuang L, Fulton RJ, Rettman P, et al. Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma. Hepatol Int. 2019;13(1):75-83. doi: 10.1007/s12072-018-9909-3

 

  1. Konjević G, Mirjačić Martinović K, Vuletić A, Babović N. In-vitro IL-2 or IFN-α-induced NKG2D and CD161 NK cell receptor expression indicates novel aspects of NK cell activation in metastatic melanoma patients. Melanoma Res. 2010;20(6):459-467. doi: 10.1097/CMR.0b013e32833e3286

 

  1. Song H, Hur DY, Kim KE, et al. IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-beta in NK cells via the c-Jun N-terminal kinase (JNK) pathway. Cell Immunol. 2006;242(1):39-45. doi: 10.1016/j.cellimm.2006.09.002

 

  1. Weiss T, Schneider H, Silginer M, et al. NKG2D-dependent antitumor effects of chemotherapy and radiotherapy against glioblastoma. Clin Cancer Res. 2018;24(4):882-895. doi: 10.1158/1078-0432.ccr-17-1766

 

  1. Okita R, Yukawa T, Nojima Y, et al. MHC class I chain-related molecule A and B expression is upregulated by cisplatin and associated with good prognosis in patients with non-small cell lung cancer. Cancer Immunol Immunother. 2016;65(5):499-509. doi: 10.1007/s00262-016-1814-9

 

  1. Chan WK, Kang S, Youssef Y, et al. A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma. Cancer Immunol Res. 2018;6(7):776-787. doi: 10.1158/2326-6066.cir-17-0649

 

  1. Wang Y, Li H, Xu W, et al. BCMA-targeting bispecific antibody that simultaneously stimulates NKG2D-enhanced efficacy against multiple myeloma. J Immunother. 2020;43(6):175-188. doi: 10.1097/cji.0000000000000320

 

  1. Basher F, Dhar P, Wang X, et al. Antibody targeting tumor-derived soluble NKG2D ligand sMIC reprograms NK cell homeostatic survival and function and enhances melanoma response to PDL1 blockade therapy. J Hematol Oncol. 2020;13(1):74. doi: 10.1186/s13045-020-00896-0

 

  1. Deng Q, Lee M, Fattah F, Koyama S, Gerber D, Akbay E. YIA23-001: Targeting NKG2D ligands is therapeutically effective in NSCLC. J Natl Comprehensive Cancer Netw. 2023;21(3.5):YIA23-001-YIA23-001. doi: 10.6004/jnccn.2022.7136

 

  1. Shen MJ, Xu LJ, Yang L, et al. Radiation alters PD-L1/ NKG2D ligand levels in lung cancer cells and leads to immune escape from NK cell cytotoxicity via IL-6-MEK/ Erk signaling pathway. Oncotarget. 2017;8(46):80506-80520. doi: 10.18632/oncotarget.19193

 

  1. Xu L, Chen X, Shen M, et al. Inhibition of IL-6-JAK/ Stat3 signaling in castration-resistant prostate cancer cells enhances the NK cell-mediated cytotoxicity via alteration of PD-L1/NKG2D ligand levels. Mol Oncol. 2018;12(3):269-286. doi: 10.1002/1878-0261.12135

 

  1. Okita R, Maeda A, Shimizu K, Nojima Y, Saisho S, Nakata M. Effect of platinumbased chemotherapy on the expression of natural killer group 2 member D ligands, programmed cell death1 ligand 1 and HLA class I in nonsmall cell lung cancer. Oncol Rep. 2019;42(2):839-848. doi: 10.3892/or.2019.7185

 

  1. Battaglia NG, Murphy JD, Uccello TP, et al. Combination of NKG2A and PD-1 blockade improves radiotherapy response in radioresistant tumors. J Immunol. 2022;209(3):629-640. doi: 10.4049/jimmunol.2100044

 

  1. Bogen JP, Carrara SC, Fiebig D, Grzeschik J, Hock B, Kolmar H. Design of a trispecific checkpoint inhibitor and natural killer cell engager based on a 2 + 1 common light chain antibody architecture. Front Immunol. 2021;12:669496. doi: 10.3389/fimmu.2021.669496

 

  1. Dougan M, Ingram JR, Jeong HJ, et al. Targeting cytokine therapy to the pancreatic tumor microenvironment using PD-L1-specific VHHs. Cancer Immunol Res. 2018;6(4):389-401. doi: 10.1158/2326-6066.cir-17-0495

 

  1. Jiang G, Ng YY, Tay JCK, et al. Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis. Cancer Immunol Immunother. 2023;72(1):223-234. doi: 10.1007/s00262-022-03247-9

 

  1. Kang TH, Mao CP, He L, et al. Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects. PLoS One. 2012;7(4):e35141. doi: 10.1371/journal.pone.0035141

 

  1. Pan M, Wang F, Nan L, et al. αVEGFR2-MICA fusion antibodies enhance immunotherapy effect and synergize with PD-1 blockade. Cancer Immunol Immunother. 2023;72(4):969-984. doi: 10.1007/s00262-022-03306-1

 

  1. Chung YM, Tsai WB, Khan PP, et al. FOXO3-dependent suppression of PD-L1 promotes anticancer immune responses via activation of natural killer cells. Am J Cancer Res. 2022;12(3):1241-1263.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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