Abstract PO-103: Cellular origin influences immune microenvironment in a pancreatic cancer mouse model with loss of Pten and activation of Kras
Bibliographic record
Abstract
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of merely 9%. Although mouse studies in the past decade have made progress towards a better understanding of how PDAC cellular origin affects tumorigenesis, there hasn’t been study on the immune microenvironment differences between precursor lesions and PDAC derived from acinar and ductal cells. Following our previous study that showed loss of Pten with oncogenic KrasG12D mutations in the ductal cells (KPtenDuct/+) resulted the formation of intraductal papillary mucinous neoplasias (IPMN) as the precursor lesion in mice, we further found siminar mutations in the acinar cells (KPtenAcinar/+) formed pancreatic intraepithelial neoplasia (PanIN) instead. We subsequently used the KPtenDuct/+ and KPtenAcinar/+ models to elucidate the effect of cellular origin on the immune microenvironment by performing immunohistochemistry. We looked at immune cell infiltration densities between precursor lesions and PDAC derived from KPtenDuct/+ and KPtenAcinar/+ models and will present the data during the conference. Additionally, macrophages polarized by conditioned media derived from KPtenDuct/+ and KPtenAcinar/+ PDAC cells showed distinctive polarization status, indicating cellular origin could result in PDAC with different cytokine and chemokine profiles that affect the immune microenvironment. Our study is the first to directly compare immune cell population between acinar- and ductal-derived PDAC originating from different types of precursor lesions with the same genetic background. Our study suggests the potential role of cellular origin on influencing PDAC immune heterogeneity. Citation Format: Yan Dou, Wesley Hunt, Justin Chhuor, Farnaz Taghizadeh, Atefeh Samani, Karnjit Sarai, Claire Dubois, David F. Schaeffer, Maike Sander, Janel L. Kopp. Cellular origin influences immune microenvironment in a pancreatic cancer mouse model with loss of Pten and activation of Kras [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-103.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".