Cited by 877Cytokine Signaling Pathways and InteractionsNF-κB Signaling PathwaysCell death mechanisms and regulation

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Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey

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Aggarwal, Bharat B., Gupta, Subash C., Kim, Ji Hye·2012·Blood

DOI 10.1182/blood-2011-04-325225PMC PMC3265196

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Abstract

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.

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Authors: Aggarwal, B. B., Gupta, S. C., & Kim, J. H.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
ORCID: Aggarwal, Bharat B.
Gupta, Subash C.
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
DOI: 10.1182/blood-2011-04-325225
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

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Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey

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