Abstract 2111: Mobilization of memory natural killer cells in cancer immunotherapy
Notice bibliographique
Résumé
Abstract Introduction: Immunological memory has long been exclusively attributed to T and B lymphocytes; however, we now know that natural killer (NK) cells also possess an analogous function. Studies of Rag-1-deficient mice (Rag1-/-), which lack T and B cells, provided evidence of NK cell-mediated immunological memory. As NK cells also possess a natural capacity to eliminate tumor cells, we set out to define the role of NK cell memory in anti-cancer immune responses using NK cell-targeted cancer immunotherapy through immunization. Methods: Rag1-/- mice (n=15) were immunized with the E749-57 RAHNIVYTIF (R9F) peptide from Human Papillomavirus 16, using the proprietary DepoVax (DPX) vaccine formulation, (IMV, Inc., NS Canada). Age-matched Rag1-/- mice (n=15) treated with the DPX vehicle alone served as controls. Sixteen days after immunization, all mice were flank-injected with C3 tumor cells, which express the R9F antigen. Tumor appearance and tumor growth rates were recorded. To test the requirement for Perforin, Rag1/Prf1/- mice (n=15) or age-matched Rag1-/- (n=15) were similarly immunized and tumor challenge. To determine the antigen specificity of NK cell memory, Rag1-/- mice (n=15) were immunized with the chicken-ovalbumin model antigen OVA257-265 SIINFEKL (DPX-SIINFEKL) or DPX vehicle (n=15). Mice for these experiments were implanted with C3 cells that express the ovalbumin gene and present the SIINFEKL antigen (C3-OVA cells). For all groups, tumor appearance and tumor growth rates were recorded. Results: Rag1-/- mice vaccinated with DPX-R9F had better protection against C3 tumor development, with 60% remaining tumor-free in comparison to the DPX vehicle control cohort, in which all mice developed tumors. Additionally, the tumor growth rate in DPX-R9F immunized mice was significantly slower than in the control cohort. Perforin has a key role in mediating the observed anti-tumor responses as Rag1/Prf1/- mice vaccinated with DPX-R9F had less tumor protection compared to the Rag1-/- mice, of which only 20% remained tumor-free. Finally, we found 60% of mice immunized with DPX-SIINFEKL and challenged with C3-OVA remained tumor-free, indicating that tumor protection could be induced by distinct antigens. Conclusions: Our preliminary results suggest that DPX-R9F or DPX-SIINFEKL immunization induces antigen-specific protection against tumor development in mice in a T cell- and B cell-independent manner. These immunizations appear to induce memory NK cells to mount antigen-specific antitumor responses that rely on Perforin as an effector molecule. By demonstrating that memory NK cells have a role in protection against tumor development, future cancer immunotherapies could be improved by priming not only T cells but also NK cells, proposing a therapeutic approach with better patient outcomes and improving, at the same time, the safety profile of these immunotherapies. Citation Format: Daniel Medina-Luna, Gayani Gamage, Michal Scur, Haggah Zein, Brendon Parsons, Andrew P. Makrigiannis. Mobilization of memory natural killer cells in cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2111.
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 | 0,001 |
| 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 ».