Abstract 6178: Photochemical immune stimulation eradicates primary tumor and induces long-lasting anti-tumor immunity in a murine cutaneous melanoma model
Notice bibliographique
Résumé
Abstract Background: Photodynamic therapy with light-activation of photosensitizers to induce cell death has been used in the treatment of various tumor types but has been ineffective to date in melanoma due to tumor pigmentation that limits the depth of light penetration. In previous studies in immunodeficient mice using a combination of tumor-cell and vascular targeting we demonstrated eradication of thin primary tumors. Here, we extend this to immunocompetent mice bearing full-thickness primary tumor, investigating both the primary and metastatic responses. Initial evidence of strong immune stimulation was also seen in multifunctional porphyrin-lipid nanoparticles (Porphysomes) as the photosensitizer. Methods: S91 tumors were induced in the flank of DBA mice by intradermal injection of 106 cells in 40µL PBS. Tumor growth was monitored by ultrasound imaging. The main treatment protocol comprised a combination of the clinical photosensitizers: chlorin e6 (1 mg/kg) plus Visudyne (0.8 mg/kg) at 1 h and 15 min drug-light intervals using light fluences of 50 J/cm2 at 670 and 690 nm, respectively. Immune biomarkers were measured in spleen, blood, tumor-draining lymph nodes and tumors at 3, 6, 12, 24, 72 h and 5 and 10 d post-treatment. The mice were monitored for 90 d to determine disease-free and overall survival. The functionality of the immune stimulation was demonstrated by tumor re-challenge, abscopal and adoptive immune transfer experiments. Initial studies were also performed using multifunctional porphyrin-lipid nanoparticles (Porphysomes, PS). Results: The dual-agent protocol resulted in disease-free and overall survival rates >95% at 90 d post-treatment. A robust immune response was triggered, with recruitment and activation of both innate and adaptive immune systems. Upon re-challenge with 106 tumor cells at 45d post primary tumor treatment, mice previously treated with PCIS showed no systemic tumor development at 30 d, confirming induction of long-lasting anti-tumor immunity. Adoptive immune transfer was demonstrated by delayed growth of primary intradermal tumor in naïve mice co-injected with splenocytes from previously-treated mice. Abscopal response was seen in mice bearing bilateral tumors when only one tumor was treated. Survival was reduced (20% at 90 d) in CD8+ T cell-depleted mice. PS-mediated treatment exhibited strong immune stimulation even at a fraction of the light dose (25 J/cm2), as measured by adoptive immune transfer and immune biomarkers. Conclusions: This study provides the first evidence that, using non-conventional treatment protocols, photodynamic tumor cell kill can eradicate primary pigmented melanoma far beyond the depth of light penetration and markedly impact systemic metastatic disease. PCIS could be used either stand-alone or an adjunctive treatment with surgery, chemotherapy and/or immunotherapy. Citation Format: Layla Pires, Carla Calcada, Tracy McGaha, Gang Zheng, Brian Wilson. Photochemical immune stimulation eradicates primary tumor and induces long-lasting anti-tumor immunity in a murine cutaneous melanoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6178.
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) | 0,001 | 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) | 0,002 | 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 ».