582 Analysis of the HR+/HER2- breast cancer tumor microenvironment following immune priming with pelareorep and atezolizumab using imaging mass cytometry – Results from the AWARE-1 trial
Bibliographic record
Abstract
Background Pelareorep (pela) is an intravenously delivered, non-modified oncolytic reovirus that shows anti-tumor activity through innate and adaptive immune responses as well as direct tumor lysis. Previous data from the window of opportunity AWARE-1 study demonstrated synergy between pela in combination with atezolizumab, demonstrating a favorable immunologic response in tumors from early breast cancer (eBC) patients.1 To understand the complex tumor microenvironment (TME) and immune responses in patients before and after treatment, we used imaging mass cytometry (IMC) to perform single cell, highly multiplexed, analysis of their tissue samples. Methods Newly diagnosed HR+/HER2- eBC patients were enrolled into two cohorts: Cohort 1: pela + letrozole (n=10); and Cohort 2: pela + letrozole + atezolizumab (n=10). Pela was administered on days 1, 2 and 8, 9, and atezolizumab was given on day 3. Tumor biopsies (FFPE samples) collected pre-treatment (D1) and on days 3 (D3, prior to atezolizumab administration) and approximately on day 21 (when tumors were surgically removed) were examined by IMC. A marker panel of 37 antibodies conjugated to a unique metal isotope was assembled. Pixel-based classification was performed in Ilastik to generate cell probability masks and processed in Cellprofiler. RStudio was used to phenotype the data with PhenoGraph. Expression and neighborhood analysis was generated in RStudio. Results Preliminary analysis with IMC reveals significant enrichment of cytotoxic T cells between D3 and surgery and between D1 and surgery. The Ki67+ subset of tumor shows a significant decrease in abundance between D1 and D3, D3 and surgery, and D1 and surgery. The general tumor subset shows a significant decrease in abundance between the D3 and surgery timepoints. Expression of PD-L1 significantly increases between the screening and D3 timepoints and significantly decreases between the D3 and surgery timepoints, conceivably explained by the immune-mediated destruction of tumor cells. Nearest neighbor distance analysis shows that cytotoxic T cells are significantly closer to tumor when comparing the screening and surgery timepoints. Conclusions In accordance with the prior AWARE-1 results, IMC demonstrated an enhanced immune state of the tumors after treatment. IMC allows us to analyze the potent immune response and cellular interactions in the TME and characterization of these complex interactions provides a better understanding of the key mechanisms of action of these treatments in order to plan future clinical trials. References Loghmani et al. SABCS 2022
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 | 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".