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Yıl 2025, Cilt: 38 Sayı: 2, 98 - 107, 30.05.2025

Duygu Kırkık , Furkan Aydın , Sevgi Kalkanlı Taş

https://doi.org/10.5472/marumj.1707952

Öz

Kaynakça

  • Murin CD. Considerations of antibody geometric constraints on NK cell antibody dependent cellular cytotoxicity. Front Immunol 2020;11:1635. doi: 10.3389/fimmu.2020.01635.
  • An Z, Flores-Borja F, Irshad S, Deng J, Ng T. Pleiotropic role and bidirectional immunomodulation of innate lymphoid cells in cancer. Front Immunol 2020;10:3111. doi: 10.3389/ fimmu.2019.03111.
  • Montazersaheb S, Fathi E, Farahzadi R. Cytokines and signaling pathways involved in differentiation potential of hematopoietic stem cells towards natural killer cells. Tissue Cell 2021;69:101501. doi: 10.1016/j.tice.2021.101501.
  • Abel AM, Yang C, Thakar MS, Malarkannan S. Natural killer cells: development, maturation, and clinical utilization. Front Immunol 2018;9:1869. doi: 10.3389/fimmu.2018.01869.
  • Roma S, Carpen L, Raveane A, Bertolini F. The dual role of innate lymphoid and natural killer cells in cancer. From phenotype to single-cell transcriptomics, functions and clinical uses. Cancers (Basel) 2021;13:5042. doi: 10.3390/ cancers13205042.
  • Roe K. Immunoregulatory natural killer cells. Clin Chim Acta 2024;546:117896. doi: 10.1016/j.cca.2024.117896.
  • Letafati A, Ardekani OS, Naderisemiromi N, et al. Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications. Virol J 2024;21:18. doi: 10.1186/s12985.024.02287-0.
  • Fu B, Tian Z, Wei H. Subsets of human natural killer cells and their regulatory effects. Immunology 2014;141:483-9. doi: 10.1111/imm.12224.
  • Deniz G, Akdis M, Aktas E, Blaser K, Akdis CA. Human NK1 and NK2 subsets determined by purification of IFN-γ-secreting and IFN-γ-nonsecreting NK cells. Eur J Immunol 2002;32:879- 84. doi: 10.1002/1521-4141(200203)32:3<879::AIDIMMU879> 3.0.CO;2-2.
  • Page A, Chuvin N, Valladeau-Guilemond J, Depil S. Development of NK cell-based cancer immunotherapies through receptor engineering. Cell Mol Immunol 2024;21:673- 87. doi: 10.1038/s41423.024.01145-x.
  • He S, Su L, Hu H, et al. Immunoregulatory functions and therapeutic potential of natural killer cell-derived extracellular vesicles in chronic diseases. Front Immunol 2023;14:1328094. doi: 10.3389/fimmu.2023.132.8094.
  • Vivier E, Rebuffet L, Narni-Mancinelli E, Cornen S, Igarashi RY, Fantin VR. Natural killer cell therapies. Nature. 2024;626(8018):711-27. doi: 10.1038/s41586.023.06945-1.
  • Forbes C, Nierkens S, Cornel AM. Thymic NK-cells and their potential in cancer immunotherapy. Immunotargets Ther 2024;13:35-47. doi: 10.2147/ITT.S441639.
  • Rascle P, Woolley G, Jost S, Manickam C, Reeves RK. NK cell education: physiological and pathological influences. Front Immunol. 2023;14:1087155. doi: 10.3389/ fimmu.2023.108.7155.
  • Fuchs S, Sawas N, Staedler N, et al. High-dimensional singlecell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis. Eur J Immunol 2019;49:462-75. doi: 10.1002/eji.201847862.
  • Charpak-Amikam Y, Lapidus T, Isaacson B, et al. Candida albicans evades NK cell elimination via binding of Agglutinin- Like Sequence proteins to the checkpoint receptor TIGIT. Nat Commun 2022;13:30087. doi: 10.1038/s41467.022.30087-z.
  • Huang X, Mo Q, Fu T, Liu Y, Diao B. STAT1 is associated with NK cell dysfunction by downregulating NKG2D transcription in chronic HBV-infected patients. Immunobiology 2022;227:152272. doi: 10.1016/j.imbio.2022.152272.
  • Lenart M, Gorecka M, Bochenej M, et al. SARS-CoV-2 infection impairs NK cell functions via activation of the LLT1-CD161 axis. Front Immunol 2023;14:1123155. doi: 10.3389/fimmu.2023.112.3155.
  • Sanz M, Madrid-Elena N, Serrano-Villar S, Vallejo A, Gutiérrez C, Moreno S. Effect of the use of Galectin-9 and blockade of the TIM-3 receptor in the latent cellular reservoir of HIV-1. J Virol 2021;95:e022014-20. doi: 10.1128/JVI.02214-20
  • Kared H, Martelli S, Tan SV, et al. Adaptive NKG2C+CD57+ natural killer cell and Tim-3 expression during viral infections. Front Immunol 2018;9:686. doi: 10.3389/fimmu.2018.00686.
  • Devulder J, Chenivesse C, Ledroit V, et al. Aberrant anti-viral response of natural killer cells in severe asthma. Eur Respir J 2020;55:1902422. doi: 10.1183/13993.003.02422-2018.
  • Li T, Cui L, Xu X, et al. The role of Tim-3 on dNK cells dysfunction during abnormal pregnancy with Toxoplasma gondii infection. Front Cell Infect Microbiol 2021;11:587150. doi: 10.3389/fcimb.2021.587150.
  • Esen F, Deniz G, Aktas EC. PD-1, CTLA-4, LAG-3, and TIGIT: the roles of immune checkpoint receptors on the regulation of human NK cell phenotype and functions. Immunol Lett 2021;240:15-23. doi: 10.1016/j.imlet.2021.09.009.
  • Uranga-Murillo I, Morte E, Hidalgo S, et al. Integrated analysis of circulating immune cellular and soluble mediators reveals specific COVID-19 signatures at hospital admission with utility for prediction of clinical outcomes. Theranostics 2022;12:290-306. doi: 10.7150/THNO.63463.
  • Zaghi E, Calvi M, Puccio S, et al. Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT. J Clin Invest 2021;6:e146973. doi: 10.1172/jci.insight.146973
  • Kim JT, Zack JA. A humanized mouse model to study NK cell biology during HIV infection. J Clin Invest 2022;132:e165620. doi: 10.1172/jci/insight165620.
  • Ty M, Sun S, Callaway PC, et al. Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria. Sci Transl Med 202315:eadd9012. doi: 10.1126/scitranslmed.add9012
  • Lu T, Ma R, Dong W, et al. Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19. Nat Commun 2022;13:2576. doi: 10.1038/s41467.022.30216-8.
  • Ma MT, Badeti S, Chen C-H, et al. CAR-NK cells effectively target SARS-CoV-2-spike-expressing cell lines in vitro. Front Immunol 2021;12:652223. doi: 10.3389/fimmu.2021.652223.
  • Lim RM, Rong L, Zhen A, Xie J. A universal CAR-NK cell targeting various epitopes of HIV-1 gp160. ACS Chem Biol 2020;15:2299-310. doi: 10.1021/acschembio.0c00537.
  • Reighard SD, Cranert S A, Rangel K M, et al. Therapeutic targeting of follicular T cells with chimeric antigen receptorexpressing natural killer cells. Cell Rep Med 2020;1:100003 doi: 10.3389/fimmu.2021.652223.

Natural killer cell therapies for non-oncological diseases: A narrative review

Yıl 2025, Cilt: 38 Sayı: 2, 98 - 107, 30.05.2025

Duygu Kırkık , Furkan Aydın , Sevgi Kalkanlı Taş

https://doi.org/10.5472/marumj.1707952

Öz

Natural killer (NK) cells represent a critical component of the innate immune system, contributing to the surveillance and elimination
of infected or aberrant cells. While, extensively studied as in the case of cancer immunotherapy as they hold potential to recognize
cancer cells without prior exposure, their potential therapeutic applications extend beyond oncology to encompass a spectrum of
non-oncological diseases. This review discusses the evolving landscape of NK cell therapies for non-oncological diseases, focusing
on their roles in infection, chronic inflammatory conditions, and autoimmune disorders. Further, this paper delves into the intricate
interplay between NK cells and immune checkpoints such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell
Ig – and mucin-domain-containing molecule-3 (TIM-3), and lymphocyte activation gene 3 (LAG3), elucidating their influence on
NK cell functionality and their implications for disease pathogenesis. Additionally, the discussion highlights the emerging paradigm
of chimeric antigen receptor natural killer (CAR-NK) cells as a promising avenue for targeted therapy in diseases such as severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV), and autoimmune disorders. By
synthesizing findings from diverse studies, it underscores the therapeutic potential of NK cell-based interventions in non-oncological
diseases. Furthermore, it encompasses the need for further research to elucidate the mechanisms underlying NK cell function in these
contexts, optimize therapeutic strategies, and translate these advancements into clinical practice.

Anahtar Kelimeler

Natural killer cell Immunotherapy Immune checkpoints CAR-NK

Kaynakça

  • Murin CD. Considerations of antibody geometric constraints on NK cell antibody dependent cellular cytotoxicity. Front Immunol 2020;11:1635. doi: 10.3389/fimmu.2020.01635.
  • An Z, Flores-Borja F, Irshad S, Deng J, Ng T. Pleiotropic role and bidirectional immunomodulation of innate lymphoid cells in cancer. Front Immunol 2020;10:3111. doi: 10.3389/ fimmu.2019.03111.
  • Montazersaheb S, Fathi E, Farahzadi R. Cytokines and signaling pathways involved in differentiation potential of hematopoietic stem cells towards natural killer cells. Tissue Cell 2021;69:101501. doi: 10.1016/j.tice.2021.101501.
  • Abel AM, Yang C, Thakar MS, Malarkannan S. Natural killer cells: development, maturation, and clinical utilization. Front Immunol 2018;9:1869. doi: 10.3389/fimmu.2018.01869.
  • Roma S, Carpen L, Raveane A, Bertolini F. The dual role of innate lymphoid and natural killer cells in cancer. From phenotype to single-cell transcriptomics, functions and clinical uses. Cancers (Basel) 2021;13:5042. doi: 10.3390/ cancers13205042.
  • Roe K. Immunoregulatory natural killer cells. Clin Chim Acta 2024;546:117896. doi: 10.1016/j.cca.2024.117896.
  • Letafati A, Ardekani OS, Naderisemiromi N, et al. Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications. Virol J 2024;21:18. doi: 10.1186/s12985.024.02287-0.
  • Fu B, Tian Z, Wei H. Subsets of human natural killer cells and their regulatory effects. Immunology 2014;141:483-9. doi: 10.1111/imm.12224.
  • Deniz G, Akdis M, Aktas E, Blaser K, Akdis CA. Human NK1 and NK2 subsets determined by purification of IFN-γ-secreting and IFN-γ-nonsecreting NK cells. Eur J Immunol 2002;32:879- 84. doi: 10.1002/1521-4141(200203)32:3<879::AIDIMMU879> 3.0.CO;2-2.
  • Page A, Chuvin N, Valladeau-Guilemond J, Depil S. Development of NK cell-based cancer immunotherapies through receptor engineering. Cell Mol Immunol 2024;21:673- 87. doi: 10.1038/s41423.024.01145-x.
  • He S, Su L, Hu H, et al. Immunoregulatory functions and therapeutic potential of natural killer cell-derived extracellular vesicles in chronic diseases. Front Immunol 2023;14:1328094. doi: 10.3389/fimmu.2023.132.8094.
  • Vivier E, Rebuffet L, Narni-Mancinelli E, Cornen S, Igarashi RY, Fantin VR. Natural killer cell therapies. Nature. 2024;626(8018):711-27. doi: 10.1038/s41586.023.06945-1.
  • Forbes C, Nierkens S, Cornel AM. Thymic NK-cells and their potential in cancer immunotherapy. Immunotargets Ther 2024;13:35-47. doi: 10.2147/ITT.S441639.
  • Rascle P, Woolley G, Jost S, Manickam C, Reeves RK. NK cell education: physiological and pathological influences. Front Immunol. 2023;14:1087155. doi: 10.3389/ fimmu.2023.108.7155.
  • Fuchs S, Sawas N, Staedler N, et al. High-dimensional singlecell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis. Eur J Immunol 2019;49:462-75. doi: 10.1002/eji.201847862.
  • Charpak-Amikam Y, Lapidus T, Isaacson B, et al. Candida albicans evades NK cell elimination via binding of Agglutinin- Like Sequence proteins to the checkpoint receptor TIGIT. Nat Commun 2022;13:30087. doi: 10.1038/s41467.022.30087-z.
  • Huang X, Mo Q, Fu T, Liu Y, Diao B. STAT1 is associated with NK cell dysfunction by downregulating NKG2D transcription in chronic HBV-infected patients. Immunobiology 2022;227:152272. doi: 10.1016/j.imbio.2022.152272.
  • Lenart M, Gorecka M, Bochenej M, et al. SARS-CoV-2 infection impairs NK cell functions via activation of the LLT1-CD161 axis. Front Immunol 2023;14:1123155. doi: 10.3389/fimmu.2023.112.3155.
  • Sanz M, Madrid-Elena N, Serrano-Villar S, Vallejo A, Gutiérrez C, Moreno S. Effect of the use of Galectin-9 and blockade of the TIM-3 receptor in the latent cellular reservoir of HIV-1. J Virol 2021;95:e022014-20. doi: 10.1128/JVI.02214-20
  • Kared H, Martelli S, Tan SV, et al. Adaptive NKG2C+CD57+ natural killer cell and Tim-3 expression during viral infections. Front Immunol 2018;9:686. doi: 10.3389/fimmu.2018.00686.
  • Devulder J, Chenivesse C, Ledroit V, et al. Aberrant anti-viral response of natural killer cells in severe asthma. Eur Respir J 2020;55:1902422. doi: 10.1183/13993.003.02422-2018.
  • Li T, Cui L, Xu X, et al. The role of Tim-3 on dNK cells dysfunction during abnormal pregnancy with Toxoplasma gondii infection. Front Cell Infect Microbiol 2021;11:587150. doi: 10.3389/fcimb.2021.587150.
  • Esen F, Deniz G, Aktas EC. PD-1, CTLA-4, LAG-3, and TIGIT: the roles of immune checkpoint receptors on the regulation of human NK cell phenotype and functions. Immunol Lett 2021;240:15-23. doi: 10.1016/j.imlet.2021.09.009.
  • Uranga-Murillo I, Morte E, Hidalgo S, et al. Integrated analysis of circulating immune cellular and soluble mediators reveals specific COVID-19 signatures at hospital admission with utility for prediction of clinical outcomes. Theranostics 2022;12:290-306. doi: 10.7150/THNO.63463.
  • Zaghi E, Calvi M, Puccio S, et al. Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT. J Clin Invest 2021;6:e146973. doi: 10.1172/jci.insight.146973
  • Kim JT, Zack JA. A humanized mouse model to study NK cell biology during HIV infection. J Clin Invest 2022;132:e165620. doi: 10.1172/jci/insight165620.
  • Ty M, Sun S, Callaway PC, et al. Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria. Sci Transl Med 202315:eadd9012. doi: 10.1126/scitranslmed.add9012
  • Lu T, Ma R, Dong W, et al. Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19. Nat Commun 2022;13:2576. doi: 10.1038/s41467.022.30216-8.
  • Ma MT, Badeti S, Chen C-H, et al. CAR-NK cells effectively target SARS-CoV-2-spike-expressing cell lines in vitro. Front Immunol 2021;12:652223. doi: 10.3389/fimmu.2021.652223.
  • Lim RM, Rong L, Zhen A, Xie J. A universal CAR-NK cell targeting various epitopes of HIV-1 gp160. ACS Chem Biol 2020;15:2299-310. doi: 10.1021/acschembio.0c00537.
  • Reighard SD, Cranert S A, Rangel K M, et al. Therapeutic targeting of follicular T cells with chimeric antigen receptorexpressing natural killer cells. Cell Rep Med 2020;1:100003 doi: 10.3389/fimmu.2021.652223.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Cerrahi (Diğer)
Bölüm Reviews
Yazarlar

Duygu Kırkık 0000-0003-1417-6915

Furkan Aydın 0009-0000-4028-523X

Sevgi Kalkanlı Taş 0000-0001-5288-6040

Yayımlanma Tarihi 30 Mayıs 2025
Gönderilme Tarihi 29 Temmuz 2024
Kabul Tarihi 12 Aralık 2024
Yayımlandığı Sayı Yıl 2025 Cilt: 38 Sayı: 2

Kaynak Göster

APA Kırkık, D., Aydın, F., & Kalkanlı Taş, S. (2025). Natural killer cell therapies for non-oncological diseases: A narrative review. Marmara Medical Journal, 38(2), 98-107. https://doi.org/10.5472/marumj.1707952
AMA Kırkık D, Aydın F, Kalkanlı Taş S. Natural killer cell therapies for non-oncological diseases: A narrative review. Marmara Med J. Mayıs 2025;38(2):98-107. doi:10.5472/marumj.1707952
Chicago Kırkık, Duygu, Furkan Aydın, ve Sevgi Kalkanlı Taş. “Natural Killer Cell Therapies for Non-Oncological Diseases: A Narrative Review”. Marmara Medical Journal 38, sy. 2 (Mayıs 2025): 98-107. https://doi.org/10.5472/marumj.1707952.
EndNote Kırkık D, Aydın F, Kalkanlı Taş S (01 Mayıs 2025) Natural killer cell therapies for non-oncological diseases: A narrative review. Marmara Medical Journal 38 2 98–107.
IEEE D. Kırkık, F. Aydın, ve S. Kalkanlı Taş, “Natural killer cell therapies for non-oncological diseases: A narrative review”, Marmara Med J, c. 38, sy. 2, ss. 98–107, 2025, doi: 10.5472/marumj.1707952.
ISNAD Kırkık, Duygu vd. “Natural Killer Cell Therapies for Non-Oncological Diseases: A Narrative Review”. Marmara Medical Journal 38/2 (Mayıs 2025), 98-107. https://doi.org/10.5472/marumj.1707952.
JAMA Kırkık D, Aydın F, Kalkanlı Taş S. Natural killer cell therapies for non-oncological diseases: A narrative review. Marmara Med J. 2025;38:98–107.
MLA Kırkık, Duygu vd. “Natural Killer Cell Therapies for Non-Oncological Diseases: A Narrative Review”. Marmara Medical Journal, c. 38, sy. 2, 2025, ss. 98-107, doi:10.5472/marumj.1707952.
Vancouver Kırkık D, Aydın F, Kalkanlı Taş S. Natural killer cell therapies for non-oncological diseases: A narrative review. Marmara Med J. 2025;38(2):98-107.
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