ArticleJCI insight2021
T cell-derived tumor necrosis factor induces cytotoxicity by activating RIPK1-dependent target cell death.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Article
- Drug-tolerant persisters and immunotherapy persister cells exhibit cross-resistance and share common survival mechanisms.Cell death and differentiation · 2026Article
- Necroptotic cell death and immunomodulator release induced by T-cell engaging anti-lymphoma therapies.Cell death & disease · 2026Article
- Antigen-directed single domain antibody-based TNFR1 agonists elicit preferential killing of HER2-overexpressing cancer cells.iScience · 2026Article
- TNF-alpha: Roles in pathogenesis and therapeutics in cancer.The Journal of biological chemistry · 2026Review
- Circulating cytokines as potential dynamic biomarkers of PD-1 blockade response and prognosis in non-small cell lung cancer.Frontiers in immunology · 2026Review
- Inhibition of TBK1/IKKε mediated RIPK1 phosphorylation sensitizes tumors to immune cell killing.Cell death discovery · 2025Article
- Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 1: their emergence from injuries to the donor organ.Frontiers in transplantation · 2025Review
- Targeting ferroptosis, pyroptosis and necroptosis for cancer immunotherapy in melanoma: mechanistic insights and clinical perspectives.Frontiers in immunology · 2025Review
- Targeting TNFR1-driven necroptosis in breast cancer.EXCLI journal · 2025Review
- Busulfan Chemotherapy Downregulates TAF7/TNF-α Signaling in Male Germ Cell Dysfunction.Biomedicines · 2024Article
- Antimelanoma Effects ofDiseases (Basel, Switzerland) · 2024Article
- p40 homodimers bridge ischemic tissue inflammation and heterologous alloimmunity in mice via IL-15 transpresentation.The Journal of clinical investigation · 2024Article
- Harnessing the Potential of Non-Apoptotic Cell Death Processes in the Treatment of Drug-Resistant Melanoma.International journal of molecular sciences · 2023Review
- Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism.Infection · 2022Review
- Necroptosis is Related to Anti-PD-1 Treatment Response and Influences the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
TNF ligation of TNF receptor 1 (TNFR1) promotes either inflammation and cell survival by (a) inhibiting RIPK1's death-signaling function and activating NF-κB or (b) causing RIPK1 to associate with the death-inducing signaling complex to initiate apoptosis or necroptosis. The cellular source of TNF that results in RIPK1-dependent cell death remains unclear. To address this, we employed in vitro systems and murine models of T cell-dependent transplant or tumor rejection in which target cell susceptibility to RIPK1-dependent cell death could be genetically altered. We show that TNF released by T cells is necessary and sufficient to activate RIPK1-dependent cell death in target cells and thereby mediate target cell cytolysis independently of T cell frequency. Activation of the RIPK1-dependent cell death program in target cells by T cell-derived TNF accelerates murine cardiac allograft rejection and synergizes with anti-PD1 administration to destroy checkpoint blockade-resistant murine melanoma. Together, the findings uncover a distinct immunological role for TNF released by cytotoxic effector T cells following cognate interactions with their antigenic targets. Manipulating T cell TNF and/or target cell susceptibility to RIPK1-dependent cell death can be exploited to either mitigate or augment T cell-dependent destruction of allografts and malignancies to improve outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.