Abstract B024: TrkB.T1 receptor promotes an immunosuppressive microenvironment driven by neutrophil recruitment in gliomas
Notice bibliographique
Résumé
Abstract Gliomas are the most common type of brain tumor in both children and adults. Communication between cancer cells and the brain tumor microenvironment (TME) is a fundamental component of brain cancer pathophysiology. Glioma cells release factors that function as chemoattractants and influence the TME. Reciprocally, the activity of neurons from the surrounding TME drives the proliferation and growth of glial malignancies through paracrine signaling, brain-derived neurotrophic factor (BDNF) being a key secreted factor. BDNF binds with high affinity to the tropomyosin receptor kinase B (TrkB). Recent work from our group has shown that the TrkB.T1 splice variant is upregulated in human gliomas. In addition, TrkB.T1 overexpression enhances the tumor aggressiveness in vivo and is associated with the downregulation of genes involved in facilitating tumor cell recognition and elimination in vitro. However, the role of TrkB.T1 splice variant in this bidirectional communication between glioma cells and the surrounding cells remains unknown. Our aim was to assess if increased levels of TrkB.T1 observed in gliomas harbor a role in modulating immune responses. Thus, we explored the immune cell heterogeneity associated with increased levels of TrkB.T1 in vivo using a glioma mouse model engineered with RCAS/tv-a technology. Tumors overexpressing TrkB.T1 show decreased overall immune infiltration but increased neutrophil recruitment. Neutrophils have been associated with unfavorable prognosis in gliomas, a decrease in the tumor-infiltrating effector lymphocytes, and worst patterns of response to immunotherapy. In fact, we also observe a decrease in the CD8+ population when TrkB.T1 is overexpressed, suggesting that TrkB.T1 might support an immunosuppressive microenvironment. Thus, we next explored in vitro the communication mechanisms associated with an increase in TrkB.T1 using 3T3 cells that were transduced with pLJM1-lentivirus to overexpress TrkB.T1. These cells were serum-starved and treated with BDNF and the conditioned media was subjected to a cytokine multiplex analysis. The results show that TrkB.T1 significantly increases key chemokine levels previously described to be involved in the recruitment of neutrophils. Taken together, this work shows that the highly expressed TrkB.T1 receptor in gliomas might support an immunosuppressive microenvironment through the recruitment of neutrophils and represents a potential target for modulating glioma-immune cell interactions needed to curb disease progression, and warrants further investigation. Citation Format: Leyre Merino-Galan, Sergio Ortiz-Espinosa, Matthew Hathaway, Ashmitha Rajendran, Hawa Larissa Jagana, Gabriel Rubio, Maryam Shabar, Noemi Reche-Ley, Siobhan S Pattwell. TrkB.T1 receptor promotes an immunosuppressive microenvironment driven by neutrophil recruitment in gliomas [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 B024.
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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 | 0,001 | 0,000 |
| 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 | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».