Abstract A047 Synergy between polarized dendritic cells, radiation and PD-1 blockade in effective treatment of rhabdomyosarcoma
Bibliographic record
Abstract
Abstract Introduction: Clinical effectiveness of immune checkpoint inhibitor (ICI) therapy depends on tumor-infiltrating cytotoxic T lymphocytes (CTLs) resulting in the need for new tools to convert “cold” tumors which lack CTLs, into CTL-infiltrated “hot” tumors. Radiation therapy (RT) is known to modulate the solid tumor microenvironment (TME) and induce a systemic immune response via enhanced tumor antigen release, production of type I interferons (IFN), intratumoral attraction and activation of DCs, and enhanced tumor recognition by natural killer (NK) cells. Thus, local irradiation of a tumor can be advantageous for both the local treatment of a tumor as well as the prevention of distant metastases. Since previous studies have shown that RT can synergize with ICI and that IL-12 producing DCs administered intratumorally also impart a clinical advantage with ICI, we tested if ST-αDC1s, a DC type designed to produce high levels of IL-12 and CTL-attracting chemokines, can enhance the combination of RT plus anti-PD-1 therapy of mouse rhabdomyosarcoma. Methods: Mice (10-15 mice per group) were inoculated with syngeneic orthotopic (gastrocnemius) M3-9-M rhabdomyosarcoma. At day 13, when tumors reached ∼200 mm3, animals started RT with single fraction of 6 Gy (225 peak kVp) using the Precision X-Rad 320 irradiator. Four doses of anti-PD-1 treatment were given on days 13, 15, 18, and 20. ST-αDC1s were given intratumorally either early (Day 13) or late (Day 20). Surviving animals were challenged with 2.5x higher number of cancer cells on day 90-100 and followed for evidence of tumor recurrence. Results: Anti-PD1 treatment alone was not effective. Control groups receiving PBS injection or anti-PD-1 alone had no survivors at day 90, with most animals succumbing to tumors within 4 weeks. RT alone improved the outcomes, yielding 15% of day-90 survivors (2/13 animals). RT plus anti-PD-1 treatment increased the fraction of survivors to 54% (7/13 animals) , while RT plus anti-PD-1 and early ST-αDC1 treatment resulted in 70% of survivors (7/10 animals). Late ST-αDC1 treatment did not enhance the survival beyond the RT plus anti-PD1 combination. The correlative studies and rechallenge studies will be presented. Citation Format: Ajay Gupta, Eoghan Connors, Michael Moser, Bryan Gillard, Katie Kokolus, Per Basse, Pawel Kalinski. Synergy between polarized dendritic cells, radiation and PD-1 blockade in effective treatment of rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A047.
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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) | 0.002 | 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 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".