Abstract 3875: Investigating tumor-immune interactions in adult sarcomas of the extremities
Notice bibliographique
Résumé
Abstract Introduction: Sarcoma is a heterogeneous group of connective tissue cancers with over 60 different subtypes. Curative treatment relies on surgical resection combined with radiation. In the event of metastasis, chemotherapy is commonly used but generally only with palliative intent. Given the heterogeneity of sarcomas, targeted therapies are limited and this has contributed to the relatively stagnant survival rates seen in the past decades. Objective: With poorly defined cancer antigens and genetic mutations, more personalized treatments, such as immunotherapy, and in particular adoptive cell transfer therapy (ACT), may be a more viable and promising option for select sarcoma patients than currently available palliative chemotherapy. As such, our study aims to create patient specific models to investigate the interactions between tumor-infiltrating lymphocytes (TILs) and autologous tumor cells. Methods: Over 250 tissue and blood samples from untreated sarcoma patients have been collected. The tissue samples are dissected and used for in vitro expansion of TILs or tumor cells. TIL cultures are characterized via flow cytometry and TIL responses are quantified using an IFNy ELISA. Tumor cultures are validated with RT-qPCR and dd-PCR to ensure tumor-specific mutations are retained. After characterizing and validating the cultures, autologous tumor cells and TILs are co-cultured to examine tumor-immune interactions. Outcomes of immune activity in the presence of tumor cells and tumorigenicity are evaluated to better understand the mechanisms that may be implicated in sarcoma immunotherapy. Results: At the end of a 3-week expansion period, of the 93 primary tumor samples cultured for TILs, only 7 did not yield any TIL growth; however, the final TIL yield varied between different patient samples, ranging from 0.005 - 83M cells. Both TIL cultures expanded from different samples of the same tumor and from tumors of different patients demonstrated variable cell proportions of CD4+ and CD8+ TILs. Some cultures also contained a proportion of CD56+ cells. ELISA documented TIL responses to stimulation in all collected cultures, indicating a viable and functional population. Of the 24 primary tumor samples cultured, 17 (8 of 10 undifferentiated pleomorphic sarcomas; 7 of 10 myxofibrosarcomas; 2 of 4 osteosarcomas) generated viable tumor cell cultures as defined by the presentation of stable growth beyond passage 5. Conclusion: Tumor cells and functional TILs can be isolated and expanded from most sarcomas; however, the methods must be optimized for each case. Further tumor culture validation by whole exome sequencing in combination with ddPCR is ongoing. A benchmark of an effective and clinically significant TIL yield will need to be better defined going forward. TILs are active in vitro and vary in population composition. Future experiments will focus on evaluating the killing capacity and tumor specificity of TILs. Citation Format: Alice Ko, Victoria Coward, Minji Lee, Kayley Xu, Nalan Gokgoz, Brendan Dickson, Jay Wunder, Irene L. Andrulis. Investigating tumor-immune interactions in adult sarcomas of the extremities [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3875.
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 | 0,001 |
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 ».