Pelareorep to promote the expression of a IFN-gamma-related gene signature that predicts response to checkpoint blockade therapy.
Bibliographic record
Abstract
3089 Background: A clinical study in patients (pts) with metastatic breast cancer (mBC) treated with pelareorep resulted in significant improvements in overall survival. Clinical studies with checkpoint blockade inhibitors (CBIs) have also resulted in noteworthy clinical responses in a small subset of mBC pts. In pts who do not respond to CBIs, the absence of IFN-γ signalling in the tumor microenvironment has been proposed as a key mediator of innate resistance. IFN-γ signalling upregulates the expression of checkpoint ligands and promotes lymphocyte activation and infiltration to the tumor microenvironment. Thus, the expression of IFN-ɣ-related genes can be used to both facilitate and predict response to CBIs. Given pelareorep’s known capacity to promote an inflamed tumor phenotype, we hypothesised that pelareorep could also stimulate the expression of IFN-ɣ-related genes associated with response to CBIs. Methods: Cell lines derived from breast cancer (BC: MCF7, T47D, MD-231), colorectal cancer (CRC: HT-29, SW620), hepatocellular carcinoma, (HCC: SNU-387) and non-small cell lung cancer (NSCLC: H522) were infected with pelareorep at a multiplicity of infection equal to 50. We examined changes in gene expression and conducted cell viability assays at 6, 12, and 18 hours post-infection (including a non-infected control). To monitor changes in gene expression we employed a 780-gene panel (nanoString) to monitor for changes in the expression of key IFN-ɣ-related and other immunity-related genes. Results: All cell lines were susceptible to pelareorep induced cytopathic effect. Strikingly, BC and HCC cells lines significantly upregulated IFN-ɣ-related genes while CRC and NSCLC cell lines demonstrated only a modest and variable ability to promote IFN-ɣ pathway activation. Moreover, BC and HCC cells lines also upregulated key chemokines that are known to promote response to immunotherapy. Conclusions: These results suggest that various tumor types are amenable to immune priming for CBIs therapy with pelareorep. The role of pelareorep in the treatment of BC and HCC deserves further investigation, particularly in combination with other immunotherapies.
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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 | 0.000 |
| 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".