ArticleOncoimmunology2016
IL12-mediated sensitizing of T-cell receptor-dependent and -independent tumor cell killing.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- High-avidity TCR signaling induces a distinct KLR-positive exhaustion state in human tumor-infiltrating CD8 T cells associated with immunotherapy response.bioRxiv : the preprint server for biology · 2026Article
- A novel anti-PD-L1/IL-8 bispecific antibody BP2402 enhances antitumor immunity and modulates inflammatory signaling in triple-negative breast cancer mice model.Journal of translational medicine · 2025Article
- The diversity of CD8Nature reviews. Immunology · 2025Review
- T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity.Journal for immunotherapy of cancer · 2025Article
- Integrating IL-12 mRNA nanotechnology with SBRT eliminates T cell exhaustion in preclinical models of pancreatic cancer.Molecular therapy. Nucleic acids · 2024Article
- Pregnancy dedifferentiates memory CD8+ T cells into hypofunctional cells with exhaustion-enriched programs.JCI insight · 2024Article
- Ovol1/2 loss-induced epidermal defects elicit skin immune activation and alter global metabolism.EMBO reports · 2023Article
- Invariant NKT cells dictate antitumor immunity elicited by a bispecific antibody cotargeting CD3 and BCMA.Blood advances · 2022Article
- The Ugly Duckling Turned to Swan: A Change in Perception of Bystander-Activated Memory CD8 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Review
- Rapid Assembly and Screening of Multivalent Immune Cell-Redirecting Therapies for Leukemia.ACS combinatorial science · 2020Article
- CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation.Frontiers in immunology · 2020Article
- Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality.Nature communications · 2019Article
- Identification of a Recombinant Human Interleukin-12 (rhIL-12) Fragment in Non-Reduced SDS-PAGE.Molecules (Basel, Switzerland) · 2019Article
- Bystander T Cells: A Balancing Act of Friends and Foes.Trends in immunology · 2018Review
- The Multi-Purpose Tool of Tumor Immunotherapy: Gene-Engineered T Cells.Journal of Cancer · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin 12 (IL12) is a key inflammatory cytokine critically influencing Th1/Tc1-T-cell responses at the time of initial antigen encounter. Therefore, it may be exploited for cancer immunotherapy. Here, we investigated how IL12, and other inflammatory cytokines, shape effector functions of human T-cells. Using a defined culture system, we followed the gradual differentiation and function of antigen-specific CD8(+) T cells from their initial activation as naïve T cells through their expansion phase as early memory cells to full differentiation as clonally expanded effector T cells. The addition of IL12 8 days after the initial priming event initiated two mechanistically separate events: First, IL12 sensitized the T-cell receptor (TCR) for antigen-specific activation, leading to an approximately 10-fold increase in peptide sensitivity and, in consequence, enhanced tumor cell killing. Secondly, IL12 enabled TCR/HLA-independent activation and cytotoxicity: this "non-specific" effect was mediated by the NK cell receptor DNAM1 (CD226) and dependent on ligand expression of the target cells. This IL12 regulated, DNAM1-mediated killing is dependent on src-kinases as well as on PTPRC (CD45) activity. Thus, besides enhancing TCR-mediated activation, we here identified for the first time a second IL12 mediated mechanism leading to activation of a receptor-dependent killing pathway via DNAM1.
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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.