Impairment of NKG2D-Mediated Tumor Immunity by TGF-β

Lazarova, Mariya; Steinle, Alexander

doi:10.3389/fimmu.2019.02689

Cited by 149Immune Cell Function and InteractionTGF-β signaling in diseasesCancer Immunotherapy and Biomarkers

Impairment of NKG2D-Mediated Tumor Immunity by TGF-β

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Lazarova, Mariya, Steinle, Alexander·2019·Frontiers in Immunology

DOI 10.3389/fimmu.2019.02689PMC PMC6873348

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Abstract

Transforming growth factor-β (TGF-β) suppresses innate and adaptive immune responses via multiple mechanisms. TGF-β also importantly contributes to the formation of an immunosuppressive tumor microenvironment thereby promoting tumor growth. Amongst others, TGF-β impairs tumor recognition by cytotoxic lymphocytes via NKG2D. NKG2D is a homodimeric C-type lectin-like receptor expressed on virtually all human NK cells and cytotoxic T cells, and stimulates their effector functions upon engagement by NKG2D ligands (NKG2DL). While NKG2DL are mostly absent from healthy cells, their expression is induced by cellular stress and malignant transformation, and, accordingly, frequently detected on various tumor cells. Hence, the NKG2D axis is thought to play a decisive role in cancer immunosurveillance and, obviously, often is compromised in clinically apparent tumors. There is mounting evidence that TGF-β, produced by tumor cells and immune cells in the tumor microenvironment, plays a key role in blunting the NKG2D-mediated tumor surveillance. Here, we review the current knowledge on the impairment of NKG2D-mediated cancer immunity through TGF-β and discuss therapeutic approaches aiming at counteracting this major immune escape pathway. By reducing tumor-associated expression of NKG2DL and blinding cytotoxic lymphocytes through down-regulation of NKG2D, TGF-β is acting upon both sides of the NKG2D axis severely compromising NKG2D-mediated tumor rejection. Consequently, novel therapies targeting the TGF-β pathway are expected to reinvigorate NKG2D-mediated tumor elimination and thereby to improve the survival of cancer patients.

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In the osteosarcoma microenvironment, NK cells were suppressed, but TGF-β expression increased.
“In the osteosarcoma microenvironment, NK cells were suppressed, but TGF-β expression increased.”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [69]
The TGF-β-Mediated Immunosuppression section says TGF-β inhibits NK-cell functions, and the NKG2D-axis section links increased tumor-associated TGF-β with impaired NK cells in several malignancies. The paper does not establish increased TGF-β expression or suppressed NK cells specifically in the osteosarcoma microenvironment (searched: osteosarcoma). No page numbers were available in our copy. (LLM, conf=0.87)
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TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
TGF-β signaling in health and disease
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Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy
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“TGFβ blocks the activation of NK cells and suppresses their cytotoxic potential by inhibiting C-type lectin receptor NKG2D expression directly and indirectly.(177) IL1 receptor-associated kinase M (IRAKM) is a potent negative regulator of Toll-like receptor (TLR) signaling and is predominantly expressed in macrophages.”
Background
Advances on immunotherapy for osteosarcoma
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The Immune Microenvironment in Pancreatic Cancer
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Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy
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Chronic inflammation, cancer development and immunotherapy
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Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions
Brauning, A., Rae, M. J., Zhu, G., Fulton, E. C., Admasu, T. D., Stolzing, A., & Sharma, A. (2022) · Cells · doi:10.3390/cells11061017 · Cited by 221 · see citing works
Designing Cancer Immunotherapies That Engage T Cells and NK Cells
Kyrysyuk, O., & Wucherpfennig, K. W. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-044122 · Cited by 215 · see citing works
TGF-β Signaling and Resistance to Cancer Therapy
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Integrins in cancer: Emerging mechanisms and therapeutic opportunities
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CAR-NK Cells in the Treatment of Solid Tumors
Wrona, E., Borowiec, M., & Potemski, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115899 · Cited by 158 · see citing works
Leveraging NKG2D Ligands in Immuno-Oncology
Fuertes, M. B., Domaica, C. I., & Zwirner, N. W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.713158 · Cited by 151 · see citing works
Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer
Sordo‐Bahamonde, C., Lorenzo‐Herrero, S., Páyer, Á. R., Gonzalez, S. R., & López‐Soto, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103726 · Cited by 123 · see citing works
Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment
Zhu, S., Wang, Y., Tang, J., & Cao, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1074477 · Cited by 127 · see citing works
Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy
Hosseini, R., Sarvnaz, H., Arabpour, M., Ramshe, S. M., Asef‐Kabiri, L., Yousefi, H., Akbari, M. E., & Eskandari, N. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01492-7 · Cited by 118 · see citing works
Follicular helper-T cells restore CD8 + -dependent antitumor immunity and anti-PD-L1/PD-1 efficacy
Niogret, J., Berger, H., Rébé, C., Mary, R., Ballot, E., Truntzer, C., Thibaudin, M., Dérangère, V., Hibos, C., Hampe, L., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002157 · Cited by 108 · see citing works
Immune Microenvironment in Osteosarcoma: Components, Therapeutic Strategies and Clinical Applications
Zhu, T., Han, J., Liu, Y., Cai, Z., Sun, W. Y., Hua, Y., & Xu, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.907550 · Cited by 113 · see citing works
Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma
Zheng, X., Jin, W., Wang, S., & Ding, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.729705 · Cited by 104 · see citing works
Cancer-associated MSC drive tumor immune exclusion and resistance to immunotherapy, which can be overcome by Hedgehog inhibition
Cascio, S., Chandler, C., Zhang, L., Sinno, S., Gao, B., Onkar, S., Bruno, T. C., Vignali, D. A. A., Mahdi, H., Osmanbeyoglu, H. U., et al. (2021) · Science Advances · doi:10.1126/sciadv.abi5790 · Cited by 101 · see citing works
The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): Emerging therapeutic opportunities
Sabit, H., Adel, A., Abdelfattah, M. M., Ramadan, R. M., Nazih, M., Abdel-Ghany, S. E., El-Hashash, A. H. K., & Arneth, B. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217865 · Cited by 101 · see citing works
Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells
Thangaraj, J. L., Coffey, M., Lopez, E., & Kaufman, D. S. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.06.009 · Cited by 82 · see citing works
Extracellular vesicles in cancer´s communication: messages we can read and how to answer
Semerádtová, A., Liegertová, M., Herma, R., Čapková, M., Brignole, C., & Zotto, G. D. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02282-1 · Cited by 89 · see citing works
NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy
Gutiérrez‐Hoya, A., & Soto‐Cruz, I. (2021) · Cells · doi:10.3390/cells10113104 · Cited by 80 · see citing works
Emerging Role of Extracellular Vesicles in Immune Regulation and Cancer Progression
Mittal, S., Gupta, P., Chaluvally–Raghavan, P., & Pradeep, S. (2020) · Cancers · doi:10.3390/cancers12123563 · Cited by 77 · see citing works
Feed-forward regulation between cellular senescence and immunosuppression promotes the aging process and age-related diseases
Salminen, A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101280 · Cited by 76 · see citing works
Autoimmunity and Cancer—Two Sides of the Same Coin
Sakowska, J., Arcimowicz, Ł., Jankowiak, M., Papak, I., Markiewicz, A., Dziubek, K., Kurkowiak, M., Kote, S., Kaźmierczak-Siedlecka, K., Połom, K., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.793234 · Cited by 73 · see citing works
Actors on the Scene: Immune Cells in the Myeloma Niche
Leone, P., Solimando, A. G., Malerba, E., Fasano, R., Buonavoglia, A., Pappagallo, F., Re, V. D., Argentiero, A., Silvestris, N., Vacca, A., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.599098 · Cited by 72 · see citing works
Arrested development: suppression of NK cell function in the tumor microenvironment
Riggan, L., Shah, S. N., & O’Sullivan, T. E. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1238 · Cited by 70 · see citing works
Natural Killer Cell Responses in Hepatocellular Carcinoma: Implications for Novel Immunotherapeutic Approaches
Mantovani, S., Oliviero, B., Varchetta, S., Mele, D., & Mondelli, M. U. (2020) · Cancers · doi:10.3390/cancers12040926 · Cited by 69 · see citing works
New Insights into the Multifaceted Role of Myeloid-Derived Suppressor Cells (MDSCs) in High-Grade Gliomas: From Metabolic Reprograming, Immunosuppression, and Therapeutic Resistance to Current Strategies for Targeting MDSCs
Lakshmanachetty, S., Cruz, J. C., Hoffmeyer, E., Cole, A. P., & Mitra, S. S. (2021) · Cells · doi:10.3390/cells10040893 · Cited by 62 · see citing works
Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade
Bozward, A. G., Warricker, F., Oo, Y. H., & Khakoo, S. I. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.643310 · Cited by 63 · see citing works
Nanomedicine-based cancer immunotherapies developed by reprogramming tumor-associated macrophages
Li, X., Guo, X., Ling, J., Tang, Z., Huang, G., He, L., & Chen, T. (2021) · Nanoscale · doi:10.1039/d0nr08050k · Cited by 58 · see citing works
Clinical perspectives on the age-related increase of immunosuppressive activity
Salminen, A. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02193-4 · Cited by 57 · see citing works
Targeting the NKG2D/NKG2D-L axis in acute myeloid leukemia
Wu, Z., Zhang, H., Wu, M., Peng, G., He, Y., Wan, N., & Zeng, Y. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111299 · Cited by 56 · see citing works
Natural Killer Cells and T Cells in Hepatocellular Carcinoma and Viral Hepatitis: Current Status and Perspectives for Future Immunotherapeutic Approaches
Kalathil, S., & Thanavala, Y. (2021) · Cells · doi:10.3390/cells10061332 · Cited by 47 · see citing works
Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients
Formenti, S. C., Hawtin, R. E., Dixit, N., Evensen, E., Lee, P., Goldberg, J. D., Li, X., Vanpouille-Box, C., Schaue, D., McBride, W. H., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0633-x · Cited by 53 · see citing works
Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells
Rabas, N., Ferreira, R. M. M., Blasio, S. D., & Malanchi, I. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00752-0 · Cited by 52 · see citing works
Natural Killer cells and monoclonal antibodies: Two partners for successful antibody dependent cytotoxicity against tumor cells
Gauthier, M., Laroye, C., Bensoussan, D., Boura, C., & Decot, V. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103261 · Cited by 50 · see citing works
Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery
Market, M., Tennakoon, G., & Auer, R. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111378 · Cited by 47 · see citing works
Multiparametric flow cytometry highlights B7-H3 as a novel diagnostic/therapeutic target in GD2neg/low neuroblastoma variants
Dondero, A., Morini, M., Cangelosi, D., Mazzocco, K., Serra, M., Spaggiari, G. M., Rotta, G., Tondo, A., Locatelli, F., Castellano, A., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002293 · Cited by 47 · see citing works
Mechanisms of NK cell dysfunction in the tumor microenvironment and current clinical approaches to harness NK cell potential for immunotherapy
Devillier, R., Chrétien, A.-S., Pagliardini, T., Salem, N., Blaise, D., & Olive, D. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.5mr0920-198rr · Cited by 44 · see citing works
Tumor-Secreted GRP78 Promotes the Establishment of a Pre-metastatic Niche in the Liver Microenvironment
Chen, L., Zheng, H., Yu, X. M., Liu, L., Li, H., Zhu, H., Zhang, Z., Lei, P., & Shen, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.584458 · Cited by 43 · see citing works
Design and Implementation of NK Cell-Based Immunotherapy to Overcome the Solid Tumor Microenvironment
Navin, I., Lam, M. T., & Parihar, R. (2020) · Cancers · doi:10.3390/cancers12123871 · Cited by 40 · see citing works
Novel role of immune-related non-coding RNAs as potential biomarkers regulating tumour immunoresponse via MICA/NKG2D pathway
Zhang, 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 38 · see citing works
Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy
Sukocheva, O. A., Неганова, М. Е., Aleksandrova, Y. R., Burcher, J. T., Chugunova, E., Fan, R., Tse, E., Sethi, G., Bishayee, A., & Liu, J. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01626-6 · Cited by 40 · see citing works
Natural killer cell-based cancer immunotherapy: from basics to clinical trials
Shi, Y., Hao, D., Qian, H., & Tao, Z. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00561-z · Cited by 41 · see citing works
The Crossroads of Periodontitis and Oral Squamous Cell Carcinoma: Immune Implications and Tumor Promoting Capacities
Elebyary, O., Barbour, A., Fine, N. A., Tenenbaum, H. C., & Glogauer, M. (2021) · Frontiers in Oral Health · doi:10.3389/froh.2020.584705 · Cited by 37 · see citing works
Treg cells promote decidual vascular remodeling and modulate uterine NK cells in pregnant mice
Hosking, S. L., Moldenhauer, L. M., Tran, H. M., Chan, H. Y., Groome, H. M., Lovell, E. A. K., Green, E. S., O’Hara, S. E., Roberts, C. T., Foyle, K. L., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.169836 · Cited by 35 · see citing works
Role of Tumor Microenvironment in Prostate Cancer Immunometabolism
Wang, Y., Chen, Y., & Wang, J. (2025) · Biomolecules · doi:10.3390/biom15060826 · Cited by 34 · see citing works
The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy
Wei, L., Xiang, Z., & Zou, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417545 · Cited by 34 · see citing works
External cold atmospheric plasma-responsive on-site hydrogel for remodeling tumor immune microenvironment
Byun, J., Wu, Y., Lee, J., Kim, J. S., Shim, G., & Oh, Y. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122162 · Cited by 33 · see citing works
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 33 · see citing works
Tumour-associated macrophages: versatile players in the tumour microenvironment
Ji, Z. Z., Chan, M. K., Chan, A. S. W., Leung, K. T., Jiang, X., To, K., Wu, Y., & Tang, P. M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1261749 · Cited by 32 · see citing works
NK and NKT Cell-Mediated Immune Surveillance against Hematological Malignancies
Shimizu, K., Iyoda, T., Yamasaki, S., Kadowaki, N., Tojo, A., & Fujii, S. (2020) · Cancers · doi:10.3390/cancers12040817 · Cited by 32 · see citing works
The evolution of cancer immunotherapy: a comprehensive review of its history and current perspectives
Ahuja, S., & Zaheer, S. (2024) · Korean Journal of Clinical Oncology · doi:10.14216/kjco.24009 · Cited by 29 · see citing works
Unravelling the Glioblastoma Tumour Microenvironment: Can Aptamer Targeted Delivery Become Successful in Treating Brain Cancers?
Giles, B., Nakhjavani, M., Wiesa, A., Knight, T., Shigdar, S. L., & Samarasinghe, R. M. (2023) · Cancers · doi:10.3390/cancers15174376 · Cited by 27 · see citing works
The mechanisms on evasion of anti-tumor immune responses in gastric cancer
Wang, J., Liu, T., Huang, T., Shang, M., & Wang, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.943806 · Cited by 28 · see citing works
NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications
Sportoletti, P., Falco, F. D., Papa, B. D., Baldoni, S., Guarente, V., Marra, A., Dorillo, E., Rompietti, C., Adamo, F. M., Ruggeri, L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136665 · Cited by 27 · see citing works
Cancer stem cell–immune cell crosstalk in breast tumor microenvironment: a determinant of therapeutic facet
Guha, A., Goswami, K. K., Sultana, J., Ganguly, N., Choudhury, P. R., Chakravarti, M., Bhuniya, A., Sarkar, A., Bera, S., Dhar, S., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1245421 · Cited by 26 · see citing works
Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma
Poorva, P., Mast, J., Cao, B., Shah, M. V., Pollok, K. E., & Shen, J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.02.043 · Cited by 26 · see citing works
Advances in Immunotherapy and the TGF-β Resistance Pathway in Metastatic Bladder Cancer
Benjamin, D. J., & Lyou, Y. (2021) · Cancers · doi:10.3390/cancers13225724 · Cited by 26 · see citing works
Nanomedicines for reversing immunosuppressive microenvironment of hepatocellular carcinoma
Pan, X., Ni, S., & Hu, K. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122481 · Cited by 25 · see citing works
Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment
Liu, Z.-L., Liu, J., Staiculescu, D., & Chen, J. (2021) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359211018026 · Cited by 24 · see citing works
Improved Relapse-Free Survival in Patients With High Natural Killer Cell Doses in Grafts and During Early Immune Reconstitution After Allogeneic Stem Cell Transplantation
Minculescu, L., Fischer‐Nielsen, A., Haastrup, E. K., Ryder, L. P., Andersen, N. S., Schjødt, I. M., Friis, L. S., Kornblit, B. T., Petersen, S. L., Sengeløv, H., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01068 · Cited by 25 · see citing works
Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression
Armitage, J. D., Newnes, H. V., McDonnell, A. M., Bosco, A., & Waithman, J. C. (2021) · Cells · doi:10.3390/cells10010056 · Cited by 24 · see citing works
Chimeric cytokine receptor TGF-β RⅡ/IL-21R improves CAR-NK cell function by reversing the immunosuppressive tumor microenvironment of gastric cancer
Ren, Y., Xue, M., Hui, X., Liu, X., Farooq, M. A., Chen, Y., Ji, Y., Duan, Y., Ajmal, I., Yao, J., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107637 · Cited by 22 · see citing works
TGF-β in tumor development and progression: mechanisms and therapeutics
Liu, J., Wang, Y., Tang, C., Zhang, L., Xiong, S., Wang, J., & Dong, C. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00403-w · Cited by 25 · see citing works
MICAgen Mice Recapitulate the Highly Restricted but Activation-Inducible Expression of the Paradigmatic Human NKG2D Ligand MICA
Kim, Y.-H., Born, C., Bléry, M., & Steinle, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00960 · Cited by 19 · see citing works
Self-citation
Osteosarcoma immune microenvironment: cellular struggle and novel therapeutic insights
Zhang, Y., Jiang, S., Lv, J., Feng, W., Yu, Y., & Zhao, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1584450 · Cited by 22 · see citing works
Immunocyte Derived Exosomes: Insight into the Potential Chemo-immunotherapeutic Nanocarrier Targeting the Tumor Microenvironment
Basak, M., Chaudhary, D. K., Takahashi, R., Yamamoto, Y., Tiwari, S., Tahara, H., & Mittal, A. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.2c00893 · Cited by 18 · see citing works
Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer
Anderson, R., Rapoport, B., Steel, H., & Theron, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511927 · Cited by 21 · see citing works
Arming cytotoxic lymphocytes for cancer immunotherapy by means of the NKG2D/NKG2D-ligand system
Lazarova, M., Wels, W. S., & Steinle, A. (2020) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2020.1803273 · Cited by 18 · see citing works
Self-citation
A Concise Review of the Role of the NKG2D Receptor and Its Ligands in Cancer
Boneva, E., Shivarov, V. S., & Ivanova, M. (2025) · Immuno · doi:10.3390/immuno5010009 · Cited by 17 · see citing works
NK/DC crosstalk-modulating antitumor activity via Sema3E/PlexinD1 axis for enhanced cancer immunotherapy
Ali, A., Alamri, A., & Hajar, A. (2024) · Immunologic research · doi:10.1007/s12026-024-09536-y · Cited by 17 · see citing works
Reduced NK Cell Cytotoxicity by Papillomatosis-Derived TGF-β Contributing to Low-Risk HPV Persistence in JORRP Patients
Wu, X., Xiao, Y., Guo, D. H., Zhang, Z., & Liu, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.849493 · Cited by 17 · see citing works
The role of NK cells in regulating tumorimmunity: current state, challenges and future strategies
Zhu, W., Fan, C., Zhao, Y., Li, W., Niu, J., Dong, S., Yang, Z., & Zhou, W. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03980-y · Cited by 17 · see citing works
Targeting NKG2D/NKG2DL axis in multiple myeloma therapy
Liu, Z., Wang, H., Liu, H., Ding, K., Shen, H., Zhao, X., & Fu, R. (2024) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2024.02.001 · Cited by 16 · see citing works
Restricted Recruitment of NK Cells with Impaired Function Is Caused by HPV-Driven Immunosuppressive Microenvironment of Papillomas in Aggressive Juvenile-Onset Recurrent Respiratory Papillomatosis Patients
Wang, W., Xi, Y., Li, S., Liu, X., Wang, G., Wang, H., Pei, M., Zhang, J., Gui, J., & Ni, X. (2022) · Journal of Virology · doi:10.1128/jvi.00946-22 · Cited by 15 · see citing works
Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia
Leifheit, M. E., Johnson, G., Kuzel, T. M., Schneider, J. R., Barker, E., Yun, H. D., Üstün, C., Goldufsky, J. W., Gupta, K. H., & Marzo, A. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179448 · Cited by 15 · see citing works
Perspective: IL-15 cytokine-armored NK cells as ready-to-use immunotherapy for diverse malignancies: therapeutic potential and toxicity risks
Baughan, S. L., Folsom, T. D., Johnson, M., Kreuger, J., Webber, B. R., & Moriarity, B. S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1704404 · Cited by 14 · see citing works
Remodeling the tumor immune microenvironment with oncolytic viruses expressing miRNAs
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NEDD8-activating enzyme inhibition potentiates the anti-myeloma activity of natural killer cells
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Authors: Lazarova, M., & Steinle, A.
Affiliations: Goethe University Frankfurt (DE)
Corresponding author: Steinle, Alexander
ORCID: Steinle, Alexander
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2019-11-15
Volume: 10
Pages: 2689-2689
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2019.02689
PMC: PMC6873348
OpenAlex: W2986121805
Cited by: 149
References: 153
Citations by year: 2026: 16 · 2025: 20 · 2024: 19 · 2023: 23 · 2022: 20 · 2021: 33 · 2020: 17 · 2019: 1
FWCI: 1.53
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Immunology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: NKG2D, TGF-beta, NKG2D ligands, tumor surveillance, tumor microenvironment, natural killer cells, cytotoxic T lymphocytes, immune evasion, cancer immunotherapy
MeSH terms: Animals, Humans, Transforming Growth Factor beta, Tumor Escape, NK Cell Lectin-Like Receptor Subfamily K, Tumor Microenvironment

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Impairment of NKG2D-Mediated Tumor Immunity by TGF-β

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