ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Enhanced IL36RN Expression and Its Association With Immune Microenvironment Predicts Poor Prognosis in Gastric Cancer.Cancer medicine · 2025Article
- The "double-edged sword" effect of cytokines in cancer: coexisting opportunities and challenges.Frontiers in immunology · 2025Review
- Abrocitinib Treatment for Localized Type of Generalized Pustular Psoriasis: A Case Report.Clinical, cosmetic and investigational dermatology · 2025Article
- FloxedCells · 2024Article
- Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023Review
- Clinical relevance and therapeutic potential of IL-38 in immune and non-immune-related disordersEuropean cytokine network · 2022Review
- Evaluating the glycolytic potential of mouse costimulated effector CD8STAR protocols · 2022Article
- Article
- Article
- Leukemic progenitor cells enable immunosuppression and post-chemotherapy relapse via IL-36-inflammatory monocyte axis.Science advances · 2021Article
- The Complex Integration of T-cell Metabolism and Immunotherapy.Cancer discovery · 2021Review
- The Role of IL-36 in Infectious Diseases: Potential Target for COVID-19?Frontiers in immunology · 2021Review
- Review
- Review
- Article
- IL36 Cooperates With Anti-CTLA-4 mAbs to Facilitate Antitumor Immune Responses.Frontiers in immunology · 2020Article
- IL-36 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
- A mathematical model of combined CD8 T cell costimulation by 4-1BB (CD137) and OX40 (CD134) receptors.Scientific reports · 2019Article
- Navigating metabolic pathways to enhance antitumour immunity and immunotherapy.Nature reviews. Clinical oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
CD134- and CD137-primed CD8 T cells mount powerful effector responses upon recall, but even without recall these dual-costimulated T cells respond to signal 3 cytokines such as IL-12. We searched for alternative signal 3 receptor pathways and found the IL-1 family member IL-36R. Although IL-36 alone did not stimulate effector CD8 T cells, in combination with IL-12, or more surprisingly IL-2, it induced striking and rapid TCR-independent IFN-γ synthesis. To understand how signal 3 responses functioned in dual-costimulated T cells we showed that IL-2 induced IL-36R gene expression in a JAK/STAT-dependent manner. These data help delineate a sequential stimulation process where IL-2 conditioning must precede IL-36 for IFN-γ synthesis. Importantly, this responsive state was transient and functioned only in effector T cells capable of aerobic glycolysis. Specifically, as the effector T cells metabolized glucose and consumed O2, they also retained potential to respond through IL-36R. This suggests that T cells use innate receptor pathways such as the IL-36R/axis when programmed for aerobic glycolysis. To explore a function for IL-36R in vivo, we showed that dual costimulation therapy reduced B16 melanoma tumor growth while increasing IL-36R gene expression. In summary, cytokine therapy to eliminate tumors may target effector T cells, even outside of TCR specificity, as long as the effectors are in the correct metabolic state.
Indexed as
Identifiers
What OpenQuestion holds
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.