IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells
Bibliographic record
Abstract
Interleukin (IL)-37 is one of the "youngest" IL-1 family members and one of the few molecules exerting anti-inflammatory activity. Upon inflammasome activation, the cytokine precursor is converted into its mature form, which acts intracellularly as a nuclear transcription factor, impairing the production of pro-inflammatory cytokines, and extracellularly by forming the IL-37/IL-18Rα/IL-1R8 complex, favoring IL-1R8 inhibitory signaling with immunosuppressive function. IL-1R8, which is mostly expressed in a number of cell types, negatively regulates both IL-1R/TLR signaling, blocking the NF-kB/JNK pathway and the production of pro-inflammatory cytokines. Owing to its ability to inhibit both innate and adaptive immunity, IL-37 has been reported to control inflammation in many chronic disorders, including cancer. IL-37 impairs the proliferation and migration of tumor cells, mediates anti-angiogenetic mechanisms, and favors immunoregulation in the tumor microenvironment (TME). This review aims to provide a current overview of IL-37 genetic and biological features and of its active interaction with IL-1R8, inducing anti-inflammatory effects on the immune system and affecting cancer cell dynamics in the TME. Moreover, it analyzes the rare pro-tumoral effects of IL-37 in some tumors and discusses their possible mechanisms. It concludes that, due to its strong anti-inflammatory property, IL-37 can be considered a potential regulator in the pathogenesis of a variety of cancers, slowing tumor progression through multiple pathways and providing valuable information for tumor immune target therapy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".