The DOI matches its Crossref record; 144 of the 144 references it cites were found in a registry or an index.
Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey
Open accessAbstract
Although activity that induced tumor regression was observed and termed tumor necrosis factor (TNF) as early as the 1960s, the true identity of TNF was not clear until 1984, when Aggarwal and coworkers reported, for the first time, the isolation of 2 cytotoxic factors: one, derived from macrophages (molecular mass 17 kDa), was named TNF, and the second, derived from lymphocytes (20 kDa), was named lymphotoxin. Because the 2 cytotoxic factors exhibited 50% amino acid sequence homology and bound to the same receptor, they came to be called TNF-α and TNF-β. Identification of the protein sequences led to cloning of their cDNA. Based on sequence homology to TNF-α, now a total of 19 members of the TNF superfamily have been identified, along with 29 interacting receptors, and several molecules that interact with the cytoplasmic domain of these receptors. The roles of the TNF superfamily in inflammation, apoptosis, proliferation, invasion, angiogenesis, metastasis, and morphogenesis have been documented. Their roles in immunologic, cardiovascular, neurologic, pulmonary, and metabolic diseases are becoming apparent. TNF superfamily members are active targets for drug development, as indicated by the recent approval and expanding market of TNF blockers used to treat rheumatoid arthritis, psoriasis, Crohns disease, and osteoporosis, with a total market of more than US $20 billion. As we learn more about this family, more therapeutics will probably emerge. In this review, we summarize the initial discovery of TNF-α, and the insights gained regarding the roles of this molecule and its related family members in normal physiology and disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“death receptors, whose activation depends on the binding of the cognate ligand(s)”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [269]
In the citing paper
“Extrinsic apoptosis is mostly driven by either of two types of plasma membrane receptors: (1) death receptors, whose activation depends on the binding of the cognate ligand(s), and (2) dependence receptors, whose activation occurs when the levels of their specific ligand drop below a specific threshold [267 269–271].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [269]
In the citing paper
“dependence receptors, whose activation occurs when the levels of their specific ligand drop below a specific threshold [267 269–271].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [269]
In the citing paper
“Death receptors include (but are not limited to): Fas cell surface death receptor (FAS; also known as CD95 or APO-1), and TNF receptor superfamily member 1A (TNFRSF1A; best known as TNFR1), 10a (TNFRSF10A; best known as TRAILR1 or DR4), and 10b (TNFRSF10B; best known as TRAILR2 or DR5) [269, 270, 272, 273].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [269]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992
RetractedMolecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729
An endotoxin-induced serum factor that causes necrosis of tumors
Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., & Williamson, B. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.9.3666 · Cited by 4,532
The TNF and TNF Receptor Superfamilies
Locksley, R. M., Killeen, N., & Lenardo, M. J. (2001) · Cell · doi:10.1016/s0092-8674(01)00237-9 · Cited by 3,650
Identification and characterization of a new member of the TNF family that induces apoptosis
Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C.-P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., et al. (1995) · Immunity · doi:10.1016/1074-7613(95)90057-8 · Cited by 2,900
Signalling pathways of the TNF superfamily: a double-edged sword
Aggarwal, B. B. (2003) · Nature Reviews Immunology · doi:10.1038/nri1184 · Cited by 2,793
Self-citationElevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure
Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007263230405 · Cited by 2,582
Inflammation: the link between insulin resistance, obesity and diabetes
Dandona, P. (2004) · Trends in Immunology · doi:10.1016/j.it.2003.10.013 · Cited by 2,170
Research works printed but not linked: 1
- Wua, 2010, Docking prediction for tumor necrosis factor-α and five herbal inhibitors., Intl J Eng Sci Technol, 2, 4263
Cited by
Sorted by citations
Items 801–876 of 876
Role and Application of Curcumin in Conventional Cancer Therapy
Pehlivanović, B., Kurtalić, L., Šapčanin, A., & Bečić, F. (2024) · World Congress on Medical Physics and Biomedical Engineering, September 7 - 12, 2009, Munich, Germany · doi:10.1007/978-3-031-49062-0_41
Pro-Inflammatory Cytokines and Post-Stroke Depression: Discussion and Thought
胡, 顺. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.141309
Kızılkaya, M. B., Öncü, Ş., Şen, S., Kaplan, A. B. U., Çelik, S., Çetin, M., & DİLSİZ, S. A. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4797567
Ge, Y., Li, P.-J., Bu, Y.-R., Zhang, B., Xu, J., He, S.-Y., Cao, Q.-L., Bai, Y., Ma, J., Zhang, L., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4353009/v1 · Cited by 1
Type I, II, and III interferon responses in the female genital tract.
Ngubane, S. B. L. (2024) · doi:10.29086/10413/23000
Lima, T. A. D. S. (2024) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2024.tde-12072024-102048
Malignancy, a real risk in patients using anti-TNF drugs for Crohn’s disease?
Díaz, K. G., Rodriguez-Paredes, G. G., Lizardo-Thiebaud, M. J., Prado-Aguirre, A., Burbano-Rodríguez, S., & Martínez‐Benítez, B. (2024) · doi:10.5348/100077z11kd2024cr
The Ligands of the Tumor Necrosis Factor Superfamily and Their Receptors
Wajant, H. (2024) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00052-1
RELT Is Upregulated in Breast Cancer and Induces Death in Breast Cancer Cells
Batiste, M., Joy, B., Yee, C. K., Cho, L., Christensen, A., Abed, I., Nguyen, K. N., Yanumula, A., Chang, H., Cho, E. D., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12122667
Inflammation, cytokines, and COVID-19 severity
Pattanayak, S. P., Sahu, R., & Sunita, P. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19170-1.00012-7
Sahu, M., Chaudhry, S., Sharma, M., Saluja, S., Jain, A., & Jain, A. (2025) · Indian Journal of Hematology and Blood Transfusion · doi:10.1007/s12288-024-01947-z
Vertebrate TNF Superfamily: Evolution and Functional Insights
Marı́n, I. (2025) · Biology · doi:10.3390/biology14010054
Fan, H., Peng, Q., Liu, T., Fang, L., Yang, C., Kong, N., Wang, L., & Song, L. (2025) · Comparative Immunology Reports · doi:10.1016/j.cirep.2025.200208
In-silico analysis of FASLG gene resistance in Cancer ImmunotherapyPreprint
Choudhury, S. (2025) · Research Square · doi:10.21203/rs.3.rs-6582476/v1
Zhao, C., Ma, X., Zhao, G., Wang, L., Li, S., & Jiang, J. (2025) · Research Square · doi:10.21203/rs.3.rs-10493392/v1
Borkar, S. A., Venturi, G. M., Chang, K.-F., Gu, J., Yin, L., Shen, J., Fischer, B. M., Nepal, U., Raplee, I., Kim-Chang, J. J., et al. (2025) · Cells · doi:10.3390/cells14161267
Zou, Y., Ren, Y., Liu, Y., Liu, J., & Chen, X. (2025) · Fitoterapia · doi:10.1016/j.fitote.2025.106860
Cytokine engineering for targeted immunotherapy
Bakhshi, P., Ho, J. Q., Zaer, N., Webster, T. J., & Zanganeh, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-21521-6.00011-9
Tnfrsf1b Protects Zebrafish Against Klebsiella pneumoniae Infection
Jing, Y., Xu, Z. Q., Ju, F., Wang, M., Tu, F., Rui, X., Cao, F., & Liu, J. (2025) · Infection and Drug Resistance · doi:10.2147/idr.s535974
Feng, T., Chen, P., & Lin, F. (2025) · Medicine · doi:10.1097/md.0000000000044916
The Interplay of Immune Response and Dental Enamel Formation in Health and Sickness
Gonçalves, J. D. L., Leme, R. D., de Sousa, J. I. T., de Queiroz, A. M., de Carvalho, F. K., & Paula‐Silva, F. W. G. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-03176-1_27
Zhang, L., Liu, J., & Hu, C. (2025) · International Journal of Polymeric Materials · doi:10.1080/00914037.2025.2543369
Insights into Transcription through Nascent RNA Sequencing.
Veloso, A. (2014) · Deep Blue (University of Michigan)
Knie, L. V., Leknes, K. N., Xue, Y., Lie, S. A., & Bunæs, D. F. (2024) · Figshare · doi:10.6084/m9.figshare.25621847
Wang, H., Wang, L., Luan, H., Xiao, J., Zhao, Z., Yu, P., Deng, M., Liu, Y., Ji, S., Ma, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26741411
Additional file 4 of ILC1-derived IFN-γ regulates macrophage activation in colon cancer
Zhang, Y., Ma, S., Li, T., Tian, Y., Zhou, H., Wang, H., & Huang, L. (2023) · Figshare · doi:10.6084/m9.figshare.24104198
Additional file 2 of ILC1-derived IFN-γ regulates macrophage activation in colon cancer
Zhang, Y., Ma, S., Li, T., Tian, Y., Zhou, H., Wang, H., & Huang, L. (2023) · Figshare · doi:10.6084/m9.figshare.24104192
Additional file 1 of ILC1-derived IFN-γ regulates macrophage activation in colon cancer
Zhang, Y., Ma, S., Li, T., Tian, Y., Zhou, H., Wang, H., & Huang, L. (2023) · Figshare · doi:10.6084/m9.figshare.24104189
Additional file 3 of ILC1-derived IFN-γ regulates macrophage activation in colon cancer
Zhang, Y., Ma, S., Li, T., Tian, Y., Zhou, H., Wang, H., & Huang, L. (2023) · Figshare · doi:10.6084/m9.figshare.24104195
Guo, Z., Qiu, C., Mecca, C. M., Zhang, Y., Bian, J., Wang, Y., Wu, X., Wang, T., Su, W., Li, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13572134
Verbascoside ameliorates liver injury by suppressing Tnfrsf1a-induced oxidative stress
Shi, R., Huang, C., Yang, H., Li, S., Liu, Z., Zhang, C., & Li, M. (2025) · Food Science and Human Wellness · doi:10.26599/fshw.2025.9250731
Qi, P., Zhou, M., Han, W., Li, H., Min, L., Li, J., Sun, Z., & Yin, H. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1693978
Tunicates have a complex, highly dynamic TNF superfamily
Marı́n, I. (2026) · PLoS ONE · doi:10.1371/journal.pone.0338039
Molecular characterization of TRADD in GIFT tilapia (Oreochromis niloticus)
Wei, Y., Tan, H., Li, J., Dai, L., GuiXiang, T., Wu, T., Wei, X., & Qi, Z. (2026) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2026.105559
Deepika, M. L. N., Gupta, A., & Pavani, C. L. (2026) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-026-00842-8
Thombare, Y. B., Tambe, S. R., & Dube, P. N. (2025) · International Electronic Conference on Synthetic Organic Chemistry (ECSOC) · doi:10.3390/ecsoc-29-26868
van Dijk, K. S. E., Begon‐Pescia, C., de Bruin, B., Özbilgiç, R., Elks, P. M., Chi, M. N., & Forlenza, M. (2026) · eLife · doi:10.7554/elife.110669
van Dijk, K. S. E., Begon‐Pescia, C., de Bruin, B., Özbilgiç, R., Elks, P. M., Chi, M. N., & Forlenza, M. (2026) · eLife · doi:10.7554/elife.110669.1
Defining the boundaries of a healthy immune response using standardized immune monitoring tools
Urrutia, A. (2017) · theses.fr (ABES) · doi:10.70675/ab3d67edz85e0z4bb0za3a8z4ce8116e8156
Importance of AJ and cell polarity in the regulation of Fas signaling
Awina, H. (2019) · theses.fr (ABES) · doi:10.70675/7b0a762dzd645z4e23z9222z2abee196c637
Target and small molecule discovery for therapeutic innovation in cardiovascular area
Liu, D. (2019) · theses.fr (ABES) · doi:10.70675/da9fa152zdcc0z498dz9194z563d22d0b77c
Role of ICOS/ICOSL in the physiology and pathophysiology of the peripheral nervous system
Barakat, R. (2020) · theses.fr (ABES) · doi:10.70675/be630417z4522z4ee7zabbaz6588cb5dec15
Mascret, A. (2020) · theses.fr (ABES) · doi:10.70675/233ae09bzdb65z4aefzb47dzfe949ddce13e
Inflammation, aging and chronic diseases : implication of inflammasomes
Guerville, F. (2023) · theses.fr (ABES) · doi:10.70675/eac3286czda71z4606z9c90z3d3efeaf1afe
Cai, M., Liu, Y., Mao, X., Wu, Y., Sun, S., Zhou, J., Huang, T., & Jiao, J. (2026) · Cell Death Discovery · doi:10.1038/s41420-026-03087-x
Liu, H., Wu, L., Chen, C., Liu, J., Li, F., & Chen, L. (2026) · BMC Immunology · doi:10.1186/s12865-026-00840-w
Saha, S., Roy, S., Chaterjee, N., & Swarnakar, S. (2025) · INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES · doi:10.55184/ijpas.v77i03.536
Genetic Evidence Linking Inflammatory Cytokines and Blood Metabolites to Heart Failure Risk
Yao, Y., Tang, L., Zhou, P., Huang, F., & Zeng, Z. (2026) · Cardiovascular Therapeutics · doi:10.1155/cdr/6340671
Wang, Y., He, Z., Yin, N., & Peng, M. (2026) · hLife · doi:10.1016/j.hlife.2026.05.003
A simple and broadly applicable nanobody-based approach to generate potent TNFR agonists
Lang, I., Zaitseva, O., Glöckler, A., Siegmund, D., Sheta, D., Mouhandes, B., Weisenberger, D., Schäfer, V., Stepanzow, S., Schneider, T., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08911-x
Nor, S. L. M., Rashid, M., Addnan, F. H., Pathmanathan, S. G., Baharom, N., Mohamad, S. N. S., Mustafar, R., Ahmad, S., Mustika, A., Fasitasari, M., et al. (2025) · Malaysian Journal of Science Health & Technology · doi:10.33102/mjosht.493
Huang, C., Yin, M., Liu, H., Jia, W., Niu, L., & Jia, M. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1848121
TNF‐α and BP180 Antibodies in Bullous Pemphigoid: Blister Fluid Dynamics and Clinical Correlations
Koska, M. C., Gürel, M. S., & Erman, H. (2026) · Dermatologic Therapy · doi:10.1155/dth/9238747
朱苡柔, Yao, H., & Xiang, W. (2026) · Clinical and Experimental Medicine · doi:10.1007/s10238-026-02194-4
Targeting lymphotoxin β receptor: from mechanism to precision therapy
Zheng, P., Dai, J., Zheng, X., & Jiang, J. (2026) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2026.2694168
Litwiniuk, A., Kalisz, M., Stępień, D., Sławkowska, N., Roszkowski, R., Remyzovska, O., Grala, B., Bik, W., & Kwiatkowski, A. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105491
Guo, Q., Li, W., Li, H., Bai, N., Huo, Y., & Zhao, H. (2026) · Cancer Plus · doi:10.36922/cp025480081
Biomarkers of Cardiovascular Stress: A Historical Review
Khosla, H., Kopel, J. J., Abohelwa, M., Awasthi, M., Mohlere, V., Singh, S. P., Shurmur, S. W., Ansari, M. A., Awasthi, Y., & Awasthi, S. (2026) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd13080358
Sun, W., Johnson, B. G., Veerasubramanian, P. K., Rockwell, K., Dickinson, T. A., Sommese, R. F., & Karlsson, F. J. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag194
Associations of Helicobacter pylori infection with NAFLD, MAFLD, MASLD, and Chinese MAFLD
Yu, H., Gao, Y., Wang, X., Chen, L., Zhang, Y., Li, H., Méndez‐Sánchez, N., & Qi, X. (2026) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848261465720
Systems-level insights into age-dependent innate immune responses in influenza B infection
Saxena, S., Kaur, G., Vishwakarma, P., Kumar, V., Kumar, A., Ompal, S., Kumar, S., Singh, S., Chauhan, A., Chaudhuri, S., et al. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.02656-25
Shi, Y., Huang, B., Liu, X., Liu, Y., Hu, Q., Lei, T., Tang, L., Xiao, G., Ning, T., Yue, S., et al. (2026) · MedComm · doi:10.1002/mco2.70153
Tamaki, M., Nakasone, H., Takano, K., Kawamura, S., Misaki, Y., Yoshimura, K., Okada, Y., Tanihara, A., Hashino, K., Yamamoto, K., et al. (2026) · British Journal of Haematology · doi:10.1111/bjh.70739
Ai, L., Li, L., Hu, L., Zhao, J., Zhou, D., Zong, F., & Yang, H. (2026) · Future Microbiology · doi:10.1080/17460913.2026.2726070
Zhuyu pill relieves cholestasis in rats by modulating the expression of lncRNAs and circRNAs
Zhang, F., Cheng, R., Zheng, Z., Xu, Z., Han, J., & Yu, H. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1744237
Lu, Y., Guo, Y., Zhang, Q., Zhang, S., Tang, W., Zhang, J., Cao, D., & Guan, M. (2026) · Journal of Hazardous Materials Advances · doi:10.1016/j.hazadv.2026.101627
BindingDB (2026) · UC San Diego · doi:10.7270/q2bv7nkg
BindingDB Entry 50046215: Discovery of highly potent TNFa inhibitors using virtual screen.
BindingDB (2016) · UC San Diego · doi:10.7270/q2k9398f
Metadata
- Authors
- Aggarwal, B. B., Gupta, S. C., & Kim, J. H.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-01-19
- Volume
- 119
- Issue
- 3
- Pages
- 651-665
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3265196
- OpenAlex
- W1989219560
- Cited by
- 877
- References
- 144
- Citations by year
- 2026: 35 · 2025: 76 · 2024: 72 · 2023: 82 · 2022: 57 · 2021: 74 · 2020: 76 · 2019: 62 · 2018: 45 · 2017: 59 · 2016: 62 · 2015: 70 · 2014: 49 · 2013: 41 · 2012: 13
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA-16 672, 16672, CA-124787-01A2)
- Genentech
- University of California, San Francisco
- National Cancer Institute (CA-16672, P01CA124787, CA-124787-01A2, P30CA016672)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- TNF-α, TNF superfamily, lymphotoxin, TNF receptor, TNF-alpha inhibitors, apoptosis, inflammation, angiogenesis, metastasis, drug development, rheumatoid arthritis, psoriasis, Crohn's disease, osteoporosis
- MeSH terms
- Humans, Neoplasms, Tumor Necrosis Factor-alpha, History, 20th Century, History, 21st Century
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
