Abstract 609: The predictive power of tertiary lymphoid structures in assessing response to trimodal therapy in muscle invasive bladder cancer
Notice bibliographique
Résumé
Abstract Introduction: Radical cystectomy is the standard of care for muscle invasive bladder cancer (MIBC). Radiotherapy (RT) is a bladder preserving option that offers patients comparable survival rates. However, up to 30% of patients require salvage cystectomy. Emerging evidence points to an important yet poorly understood link between response to RT and the tumor microenvironment (TME). Notably, tertiary lymphoid structures (TLS) are being investigated as a potential local hub for mounting an immune response. These lymph-node-like structures are highly organized with a B cell zone surrounded by T cells. Mature TLS also have an active germinal center (GC) with follicular dendritic cells. A number of studies correlated TLS with improved outcomes in several types of solid cancers. Here, we explore the use of TLS and its associated immune TME as a predictive biomarker for response to RT in MIBC. Methods: Hematoxylin and Eosin (H&E) stained formalin-fixed-paraffin-embedded sections of pre-RT biopsy from 147 MIBC patients were examined to identify TLS presence with confirmation from a pathologist. Subsequent multiplex immunohistochemistry (mIHC) staining with CD21 and CD23 characterized TLS maturity. To investigate the interaction between TLS and TME, tissue microarrays (TMAs) were constructed, and gene expression profiles were obtained for 106 patients using NanoString’s Digital Spatial technology. Moreover, the TMAs were stained with CD20, Neutrophil Elastase, CD68, CD8, CD4, and FoxP3 by mIHC. Image analysis was performed on the Halo platform. TLS gene signature was correlated to the immune infiltration and the patient outcomes. Results: H&E revealed that 19.7% of patients (n=68) had TLS with a GC, 17.0% (n=25) had TLS without a GC, and 12.9% (n=19) had no TLS. In the remaining 50.3% of cases (n=74), confirmation of TLS presence required staining with CD3 and CD20. Gene expression of TLS marker CXCL13 was higher among complete responders to RT (p-value=0.0440). This trend was weakened when we examined a previously described 12-chemokine TLS signature (p= 0.1506). When segregating patients into TLS high/TLS low groups based on the gene signature, we observed significantly higher infiltration of CD8+ T cells (p<0.0001), neutrophils (p=0.005), regulatory T cells (p=0.0278), and B cells (p=0.0247) among the TLS high group. No difference in macrophage infiltration was observed between the two groups.Conclusion: Our results point to a nuanced role of TLS in the context of response to RT and in relation to the TME. Further histological analysis of TLS characteristics is necessary to paint a picture of the different immune profiles we observe in our cohort and their association with the outcomes of RT. Overall, our study could identify an immune signature that could serve as a selection criterion for patients who would benefit the most from bladder-sparing therapies. Citation Format: Nour Hassan, José Joao Mansure, Mina Farag, Ronald Kool, Eva Michaud, Mohanned Alessa, Luis Souhami, Fabio Cury, Fadi Brimo, Wassim Kassouf. The predictive power of tertiary lymphoid structures in assessing response to trimodal therapy in muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 609.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».