Abstract 5218: Boosting doxorubicin-induced immunogenic cell death by using tumor microenvironment modulating nanoparticles
Notice bibliographique
Résumé
Abstract Background: Immunogenic cell death (ICD) is a cell death modality which triggers an immune response against dead-cell antigens, particularly when they derive from cancer cells. ICD has been reported to be highly induced by anthracycline drugs, such as doxorubicin (DOX), via facilitating tumor antigen presentation to and activation of T cells. However, these immunogenic effects may be compromised due to the immunosuppressive tumor microenvironment (TME), such as excess ROS, particularly H2O2, produced by tumor cells and dysfunctional macrophages in the tumor. We hypothesize that modulating immunosuppressive factors in the TME can enhance tumor response to chemotherapy and boost immunity. Specifically, polymer-lipid encapsulated manganese dioxide nanoparticles (PLMD NPs) are used to reduce tumor hypoxia and ROS by scavenging H2O2 and generating oxygen. Antitumor immunity against the cancer cells can be enhanced by the combination therapy with PLMD and DOX. Methods: PLMD NPs were prepared by dispersing MnO2 precursor particles in melted lipid and polymer in a surfactant-containing aqueous medium. The efficacy of the combination treatment was evaluated in immunocompetent mice-bearing orthotopic murine EMT6 breast tumor. The mice were treated by intravenous (IV) injection of free DOX alone, or 4 h after PLMD NP IV injection. A re-challenge study was performed by re-inoculating EMT6 cells in cured mice 120 days after the initial treatments. to validate the presence of adaptive anti-tumor immunity in the animals treated with PLMD+DOX combination, splenocyte transfer study was carried out. Ex-vivo imaging techniques were used to measure the number of infiltrated CD8+ T cells into the tumor and polarization of the M2 to M1 macrophages. Results: The PLMD+DOX combination treatment resulted in the median survival time by ~ 5.6-fold as compared to DOX alone, and led to 60% cure rate (9 out of 15 mice). This combination therapy also generated anti-tumor immunity against tumor re-inoculation in 88% of surviving mice and provided anti-tumor immunity in naïve mice that received splenocyte transfer with 57% of mice without tumor growth after inoculation. Ex-vivo studies resulted a 400% increase in the number of intratumoral CD8+ T cells, 5 days after PLMD+DOX treatment, while DOX alone treatment showed only 150% increase when compared to saline treatment. Moreover, M1 macrophages-related CD86 positive cells were found up-regulated by 51% while a significant loss of M2 marker CD163 (-47%) was observed in PLMD+DOX-treated tumors compared to DOX alone-treated ones. Conclusions: The present work demonstrated that clinically suitable PLMD NPs can effectively downregulate TME-associated immunosuppression factors and boost DOX efficacy. The PLMD NPs and DOX combination therapy presents a multimodal and a translational treatment approach to enhancing DOX-induced ICD and boosting anti-tumor immunity. Citation Format: Mohammad Ali Amini, Azhar Abbasi, Ping Cai, Hoyin Lip, Jason Li, Claudia Gordijo, Li Zhang, Michael Rauth, Xiao Yu Wu. Boosting doxorubicin-induced immunogenic cell death by using tumor microenvironment modulating nanoparticles [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 5218.
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) | 0,002 | 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 ».