Abstract B035: The contribution of inflammasomes and cGAS-STING in RT-induced cell fate
Bibliographic record
Abstract
Abstract Radiotherapy (RT) is a curative treatment modality for many solid cancers. Our group has previously demonstrated that activation of the cGAS-STING pathway by RT induces inflammatory cytokine production and subsequent stimulation of anti-tumour immunity in concert with immune checkpoint blockade treatment. We have identified three other proteins that contribute to inflammatory signalling after RT: AIM2 (Absent in Melanoma 2), NLRP3 (NOD-Like Receptor Pyrin Domain-Containing 3), and IFI16 (Interferon Gamma Inducible Protein 16). Each of these proteins contribute to form distinct protein complexes called inflammasomes that, like cGAS-STING, sense cytoplasmic DNA. Little is known about how inflammasome signalling may change after RT, or how inflammasomes may influence RT-ICB induced anti-tumour immunity. We hypothesize that RT induces inflammasome signalling to influence specific gene expression and cytokine profiles, in tandem with alterations in cellular fate with implications for systemic anti-tumour immunity triggered by radiotherapy. We will present ongoing work in which we show that pharmacological or genetic disruption of inflammasomes alters cytokine production post-RT. We also demonstrate that manipulation of cell fate through senolytic therapy or manipulation of caspase activity alters the balance of cytokine production post-RT. Together our data strongly implicates the role of several inflammasome complexes in the response of epithelial cells to RT. Our work will also highlight the possible crosstalk between the cGAS-STING pathway and inflammasome complex pathway, both triggered by RT. Understanding and subsequent manipulation of cell fate, in part through inflammasome and cGAS-STING mediated activity, may be a therapeutic strategy to influence treatment responses, such as anti-tumour immunity, in cancer. Citation Format: Cindy T Ha, Shirony Nicholson-Puthenveedu, Shane M Harding. The contribution of inflammasomes and cGAS-STING in RT-induced cell fate [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B035.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".