Abstract 2524: Investigating the role of neutrophils in muscle-invasive bladder cancer and response to radiation therapy
Notice bibliographique
Résumé
Abstract Background: Radiation therapy (RT) is an increasingly used bladder-sparing therapy for patients with muscle-invasive bladder cancer (MIBC). However, 20-30% of patients do not respond to RT. Neutrophils have previously been linked to radioresistance, but the specific mechanism is still unknown. Previous work by our team has shown that neutrophil extracellular trap (NET) formation plays a role in RT resistance in an immunologically hot tumor, with high T cell infiltration, using the MB49 murine bladder cancer cell line, in a vivo model. In MIBC, a recently developed cell line can be used to study cold, luminal-like tumors. However, work on this cell line and its response to RT is still in its initial stages. Immune checkpoint inhibitors such as anti-PD-L1 have been tested by our team in these cold tumors of MIBC and have not shown to be effective in treating or radiosensitizing the tumor. Consequently, we aim to determine how neutrophil migration and neutrophil extracellular traps (NET) impact tumor growth in a cold, luminal-like tumor model. Furthermore, we aim to understand how neutrophil migration and NETs impact immunological changes in the tumor microenvironment (TME). Methods: To determine the response to RT in these cold tumors, mice were injected with 5M cells on the right flank of our luminal-like cancer model (UPPL cell line). Once tumors reached 0.1-0.15 cm3, mice were randomized into the different treatment groups: 1) Control; 2) RT; 3) Anti-PDL1 4) DNAse I; 5) RT + Anti-PDL1; 6) RT + DNAse I; 7) Anti-PDL1 + DNAse I; 8) RT + Anti-PDL1 + DNAse I. Size of the tumor was monitored. 8 mice tumors per group were collected at the primary endpoint set at 1.5 cm3 and 5 mice tumors per group were collected after 21 days (midpoint). Tumors were collected analyzed by flow cytometry and immunohistochemistry (IHC). Preliminary Results: Prolonged survival was observed in the mice treated with the triple combination when compared to the other groups. Tumor growth in this group also showed delay early on. So far, the frequency of pro-tumorigenic neutrophils infiltration in tumors seems to happen early on (midpoints) in mice treated with RT, whereas the infiltration happens later (endpoint) in the mice treated with the triple combination. Currently, we are also evaluating the NET production in these tumors through IHC. Conclusion: This ongoing experiment using RT on the UPPL cell line will allow us to understand what happens in patients who are resistant to RT. Understanding the role of neutrophils and NETs, along with the changes in the TME caused by the manipulation of these is key to understanding radiation resistance. This knowledge will bring us one step closer to developing new bladder-sparring treatments and improving patient care in the clinic. Citation Format: Sabina Fehric, Eva Michaud, Surashri Shinde-Jadhav, JiaMin Huang, Jose J. Mansure, Roni Rayes, Jonathan Spicer, Wassim Kassouf. Investigating the role of neutrophils in muscle-invasive bladder cancer and response to radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2524.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,001 |
| 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 ».