Abstract 4056: Immune regulation by miR-1227 LO
Notice bibliographique
Résumé
Abstract Immunotherapy offers great promise for the treatment of prostate cancer; however prostate cancer often acquires mechanisms to dampen the tumoricidal immune response. Understanding how prostate cancer dampens the immune system will facilitate the generation of more effective immunotherapies. Here we investigate how large oncosomes (LO)-mediated transfer of miR-1227 to immune cells modulates the immune response. Extracellular vesicle (EV)-encapsulated miRNAs are being increasingly recognized for playing a key role in cancer progression and immune modulation. miR-1227 is a poorly characterized miRNA that is enriched in EV secreted by prostate cancer cells in comparison to non-malignant prostate epithelial cells. miR-1227 expression is increased in migratory glioblastoma cells in comparison to non-migratory glioblastoma cells, and in radiation resistant esophageal cells and colorectal cancer stromal cells indicating that miR-1227 is upregulated in different cancer types. However, the role of miR-1227 in cancer is poorly understood. We demonstrate here that EV obtained from prostate cancer cells overexpressing miR-1227, induce the migration of prostate cancer cells and fibroblasts. A comparative analysis between different EV subtypes indicates that miR-1227 is enriched in LO, a class of EV that are secreted by highly invasive amoeboid-migrating cells. We also show that LO carry more RNA than the more widely studied exosomes indicating that LO may be a more robust source of EV-encapsulated miRNA. RNA sequencing from miR-1227 stably expressing prostate cancer cells and 5 different in silico miRNA target prediction methods were used to identify putative miR-1227 targets. IPA pathway analysis from these predicted targets highlighted several functions related to the immune system, including T cell homeostasis, T cell development, and development of Th17 cells. A more in-depth analysis of the 51 genes involved in T cell homeostasis showed enrichment of genes associated with Th17 and Th1 T cell differentiation. Alterations in Th17 and Th1 differentiation modulates T cell cytokine secretion, which are important mediators of cancer growth and progression. Transient transfection of miR-1227 in immune cells altered the cytokine expression profile, resulting in the upregulation of several cytokines that promote cancer growth including CCL5 and IL6. We tested whether LO can be taken up by activated T cells to directly modulate cytokine secretion. To determine whether miR-1227 can be functionally transferred to recipient cells via LO we isolated LO from prostate cancer cells stably expressing miR-1227 using ultracentrifugation followed by density gradient purification. The isolated LO were used to treat immune cells to show that LO-encapsulated miR-1227 alters cytokine profiles. These results indicate that LO-encapsulated miR-1227 may be involved in cancer immune modulation through targeting specific genes involved in T-cell differentiation. Citation Format: Andrew R. Chin, Dolores Di Vizio, Valentina R. Minciacchi, Mariana Sobreiro, Cristiana Spinelli. Immune regulation by miR-1227 LO [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4056.
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,002 |
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 ».