Abstract IA03: Therapeutic modulation of nucleic acids-induced immune activation
Bibliographic record
Abstract
Abstract Mechanisms of defense against nucleic acids are central to maintaining genome integrity and have evolved to sense multiple nucleic acids alterations in structure and/or location within a cell. In cancer, dysregulation of DNA repair pathways and gene transcription are common and are associated with cellular stress and innate immune signaling, thus promoting immune surveillance. Subversion of such responses is often required for a cancer to evade immune control and progress to become clinically significant. One example is the epigenetic silencing of stimulator of interferon genes (STING), which is activated by cGAMP produced by the cyclic GMP-AMP synthase (cGAS) after sensing cytosolic DNA. Importantly, therapeutic interventions, such as radiation therapy, can leverage these hard-wired nucleic acids defense pathways to induce anti-tumor immune responses. Extensive preclinical data demonstrate that induction of interferon type I (IFN-I) in cancer cells and the tumor microenvironment by radiation promotes antigen presentation and recruitment of T cells and plays a central role in the ability of radiation to synergize with immune checkpoint inhibitors. In the clinic, however, such effects of radiation have not been consistently observed in unselected patient populations. This highlights the need for an improved understanding of the complex cross-talk between radiation-induced DNA damage response and innate immune signaling, and their alterations in cancer. We are currently investigating the interplay between cGAS/STING pathway and the ectonucleotidases that convert pro-inflammatory signals generated by radiation into immunosuppressive adenosine. The latter offers candidate actionable targets to improve radiation-induced immune activation. Overall, insights into the fundamental mechanisms that couple DNA damage with innate immune signaling will enable the fine tuning of therapeutic interventions that promote anti-tumor immune responses. Citation Format: Sandra Demaria. Therapeutic modulation of nucleic acids-induced immune activation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr IA03.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".