Abstract A010: Assay development to assess the efficiency and stability of candidate molecules for transcriptional gene silencing of FOXP3, using a human tumor-derived cell line
Notice bibliographique
Résumé
Abstract Regulatory T cells play an important role to modulate the balance between immunotolerance and immunosurveillance. These cells have the property of inhibiting effector lymphocytes and may antagonize antitumor immunity. Regulatory T cells are originated in the thymus, or even converted from peripheral lymphocytes by factors produced in the tumor microenvironment. Clinical data suggests that regulatory T cell infiltration correlates with poor prognosis in the treatment of solid tumors. The FOXP3 transcription factor is considered a master key to control the phenotype of regulatory T cells. It was previously shown, that the ectopic expression of FOXP3 can induce an immunosuppressive phenotype in lymphocytes. In contrast, it has been observed that mutations in the FOXP3 gene can cause impaired immunosuppressive activity mediated by regulatory T cells, such as the autoimmunity syndrome known as IPEX. In this sense, the FOXP3 transcription factor may be an interesting target, looking for inactivation of the immunosuppressive phenotype of regulatory T cells, to potentiate antitumor response. In this work, we present an assay development to investigate the potential of transcriptional interference RNA candidates to silence FOXP3 expression. In contrast to post-transcriptional gene silencing method, which targets messenger RNA and depends on a constant supply or efficient turn-over of the inhibitory molecule, the transcriptional gene silencing targets the cellular DNA genome, inducing epigenetic changes that may control the target gene transcription. We employed the human MCF-7 tumor cell line, which has endogenous and constitutive expression of FOXP3 as a target model to test transcriptional gene silencing candidates. This cell line is transduced with lentiviral vectors harboring interfering RNA sequences driven to the FOXP3 promoter region. The RNA interference candidates are then evaluated for their ability to induce DNA methylation, by bisulfite method, and transcriptional gene silencing of FOXP3, by qPCR. We performed the screening of candidates for FOXP3 transcriptional silencing, in comparison to a post-transcriptional interference RNA control. The lentiviral transduced cells are easily expanded and allow a temporal analysis of target gene expression. In this model, we observed the possibility of finding transcriptional interference RNA candidates that exhibited high efficiency and stability, that may be used for research purposes, or even for the investigation of new therapeutic possibilities in immuno-oncology. Citation Format: Carolinne T Fogagnolo, Daniela S Mizobuti, Marcio C Bajgelman. Assay development to assess the efficiency and stability of candidate molecules for transcriptional gene silencing of FOXP3, using a human tumor-derived cell line [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A010.
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 | 0,004 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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 ».