<i>In Situ</i> Vaccination after Accelerated Hypofractionated Radiation and Surgery in a Mesothelioma Mouse Model
Bibliographic record
Abstract
Abstract Purpose: How best to sequence and integrate immunotherapy into standard of care is currently unknown. Clinical protocols with accelerated nonablative hypofractionated radiation followed by surgery could provide an opportunity to implement immune checkpoint blockade. Experimental Design: We therefore assessed the impact of nonablative hypofractionated radiation on the immune system in combination with surgery in a mouse mesothelioma model. Blunt surgery (R1 resection) was used to analyze the short-term effect, and radical surgery (R0 resection) was used to analyze the long-term effect of this radiation protocol before surgery. Results: Nonablative hypofractionated radiation led to a specific immune activation against the tumor associated with significant upregulation of CD8+ T cells, limiting the negative effect of an incomplete resection. The same radiation protocol performed 7 days before radical surgery led to a long-term antitumor immune protection that was primarily driven by CD4+ T cells. Radical surgery alone or with a short course of nonablative radiation completed 24 hours before radical surgery did not provide this vaccination effect. Combining this radiation protocol with CTLA-4 blockade provided better results than radiation alone. The effect of PD-1 or PD-L1 blockade with this radiation protocol was less effective than the combination with CTLA-4 blockade. Conclusions: A specific activation of the immune system against the tumor contributes to the benefit of accelerated, hypofractionated radiation before surgery. Nonablative hypofractionated radiation combined with surgery provides an opportunity to introduce immune checkpoint blockades in the clinical setting. Clin Cancer Res; 23(18); 5502–13. ©2017 AACR.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".