Abstract A004: Radiation-induced changes to the immune microenvironment in an immunocompetent mouse model of Ewing sarcoma
Notice bibliographique
Résumé
Abstract Background: Ewing sarcoma is a rare, aggressive, fusion oncoprotein-driven pediatric cancer. Patients with upfront metastatic or surgically unresectable disease commonly undergo radiation as part of standard of care therapy. Currently, little is known about the effect of radiation specifically on the immune microenvironment of Ewing tumors, as no routine biopsies or other clinical samples are acquired during radiation. Further, historically, the field has lacked an immunocompetent mouse model of Ewing sarcoma in which to study Ewing tumor-immune cell interactions. Given our interest in understanding the anti-tumor immune response specifically during times of DNA damage, we sought to model Ewing sarcoma in a humanized mouse model (where human immune cell interactions with human tumor cells can be examined) in order to examine the Ewing tumor immune microenvironment (TIME) during radiation. Here, we determine the likeness of our established humanized mouse model of Ewing sarcoma to that of human Ewing tumors at baseline and examine changes in the Ewing TIME upon delivery of radiation. Methods: Blood from humanized NSG mice was analyzed by flow cytometry to confirm human immune cell reconstitution. Human Ewing tumor cells were injected into humanized mice and allowed to grow for approximately three weeks. Tumors were treated with radiation (either single dose or fractioned doses x 5 days) using the MultiRad350 Precision irradiator and lead shields were used to isolate the tumor area in the radiation field. Immune cells infiltrating tumors with/without radiation exposure were subsequently analyzed by multiplexed immunohistochemistry, flow cytometry, PCR, and RNAseq analysis. Ewing tumor immune infiltrates (as baseline/without radiation) from humanized mice models were compared to that of patient Ewing tumors. Results: Ewing tumors from both established and primary cell lines were successfully established in humanized mice. Similar to patient primary Ewing tumor samples, local Ewing tumors in humanized mice demonstrate a proportion of T-cell infiltration, although the overall number of infiltrating immune cells is low. Macrophage populations in Ewing sarcoma are not as predominant as in tumors such as osteosarcoma and are represented in this model. Analyses detailing the spatial localization and transcriptional profiles of Ewing tumor immune infiltrates following radiation are ongoing. Conclusions: In the absence of syngeneic and transgenic models of Ewing sarcoma, the use of humanized mouse models is a feasible alternative to address specific questions regarding the Ewing sarcoma TIME. Understanding the Ewing immune microenvironment during radiation therapy, a commonly used treatment modality in Ewing sarcoma, provides clues as to promising agents that may be worthy of preclinical testing to enhance the anti-tumor immune response during radiation in high-risk patients. Citation Format: Jessica D. Daley, Elina M. Mukherjee, Anthony R. Cillo, Adriana C. Tufino, Nathanael G. Bailey, Tullia C. Bruno, Linda M. McAllister-Lucas, Dario A. Vignali, Kelly M. Bailey. Radiation-induced changes to the immune microenvironment in an immunocompetent mouse model of Ewing sarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A004.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».