Abstract A038: Antigen Presentation By Cancer-Associated Fibroblasts
Bibliographic record
Abstract
Abstract Introduction: Immunotherapy has shown promise in treating some patients with metastatic diseases, but the effectiveness of the immune system in controlling cancer is hampered by a suppressive tumor microenvironment (TME), in which cancer-associated fibroblasts (CAFs) play a key role. Developing new and highly specific immunotherapeutic tools targeting CAFs may have a significative impact on tumor control. For this purpose, we aim to investigate antigen presentation characteristics by MHC-I molecules in CAFs and identify targetable CAF-specific antigens. Methods and Results: Analysis of existing single-cell datasets revealed higher expression of MHC-I in CAFs compared to normal fibroblasts (p<0.05) in various tumor types. In melanoma, higher MHC-I expression was linked to resistance to immune checkpoint blockade (ICB). Additionally, we found a positive correlation between MHC-I expression and immunosuppressive molecules such as galectin-9 and HVEM. These observations were supported by initial flow cytometry analyses in CAF cell lines derived from patients. Furthermore, prolonged and severe hypoxia further elevated MHC-I protein levels in CAF cell lines. Using a proteogenomic approach with mass spectrometry, we identified over 10,000 antigens in five patient-derived CAF cell lines from primary breast cancer tumors and one normal fibroblast cell line. By integrating single-cell and bulk RNA sequencing data from various tumors and normal tissues, we identified more than 20 CAF-specific or fibroblast-specific antigens. Conclusion: CAFs exhibit high MHC-I expression, which is amplified under hypoxic conditions. We have identified CAF-specific antigens that require evaluation for their immunogenicity, indicating the potential of CAFs as targets for antigen-based therapies. Citation Format: Eralda Kina, Caroline Côté, Jean-David Larouche, Chantal Durette, Joel Lanoix, Eric Bonneil, Jean-Philippe Laverdure, Gabriel Ouellet Lavallée, Margaret Buchanan, Adriana , Fatima Mechta-Grigoriou, Pierre Thibault, Mark Basik, Claude Perreault. Antigen Presentation By Cancer-Associated Fibroblasts [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A038.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".