Abstract PO-082: Antigen presentation and inflammatory effects on immune surveillance: Window of opportunity metformin monotherapy trial for squamous cell carcinoma of the head and neck (HNSCC)
Notice bibliographique
Résumé
Abstract Introduction: The tumor microenvironment frequently displays dysregulated cellular metabolism, which contributes to aggressive behavior of the tumor. Though the mechanism of effect is unclear, clinical data suggest an association between metformin and improved outcomes in head and neck squamous cell carcinoma (HNSCC). The aim of this study is to investigate post-metformin treatment effects on the tumor microenvironment (TME) of HNSCC by using spatial RNA sequencing data from a metformin monotherapy window-of-opportunity clinical trial. Methods: This was a single-center prospective clinical trial of metformin in patients with HNSCC and a plan for definitive surgical resection. Primary lesions were biopsied prior to treatment and compared to matched post-treatment surgical specimens. Following biopsy-proven HNSCC diagnosis, metformin was initiated at 500 mg/day and increased to 1,000 mg twice daily by day 6. Spatial RNA sequencing of 18,000+ genes in CD45, CD163, and PanCK segments was conducted using Nanostring’s GeoMx digital spatial profiling (DSP). Sequencing data was analyzed by using unbiased gene set enrichment analysis (GSEA) and reported as a rank in gene list from 18,000+ total genes for post- vs pre-treatment analyses. Results: In all HPV positive, post-treatment samples in all three segments, GSEA demonstrated enrichment of antigen presenting cell types including NK cells, monocytes, and dendritic cells (q< 0.001). Inflammatory and metabolism signatures (IFN-y, IFN-a, oxidative phosphorylation) were enriched after metformin monotherapy in HPV+ samples within the PanCK positive segment (q< 0.001). Epithelial mesenchymal transition (EMT) was noted to be positively enriched while plasma cell signatures were negatively enriched within in HPV- post-treatment samples in the CD163 segment (q< 0.001). Within the CD45 positive segment, enriched expression of mRNAs for ribosomal-protein subsets were noted in T-cell gene sets and not in B-cell gene sets; in the CD45 segment, cytoplasmic ribosomal proteins is the second-most enriched gene set from C2 canonical pathways gene sets. Conclusion: Antigen presentation, inflammation, and ribosomal protein encoding genes were enriched with metformin monotherapy in the window of opportunity setting for HNSCC. Ribosomal proteins may also play a role in antigen presentation and immune surveillance in the post-treatment setting. Further research is required to describe the TME effects of metformin monotherapy and its effects on treatment response. Citation Format: Derek S. Mann, Sruti Tekumalla, Amiti Jain, Jacob Riordan, Alban Linnenbach, Diana Menezes, Ubaldo Martinez-Outschoorn, Joseph M. Curry. Antigen presentation and inflammatory effects on immune surveillance: Window of opportunity metformin monotherapy trial for squamous cell carcinoma of the head and neck (HNSCC) [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-082.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».