Abstract CT263: Atezolizumab clinical trial biopsies reveal varied immune landscapes in clear cell sarcoma and chondrosarcoma
Notice bibliographique
Résumé
Abstract Introduction: Clear cell sarcoma (CCS) constitutes <1% of sarcomas and frequently presents in adolescents and young adults. Chondrosarcoma is one of the most common bone malignancies in adults, occurring as conventional chondrosarcoma (CS) or the more-aggressive dedifferentiated chondrosarcoma (dCS). There is no standard of care therapy approved for these malignancies. The activity of immune checkpoint inhibition (ICI) in alveolar soft part sarcoma, together with case reports of ICI activity in these other sarcoma subtypes, prompted us to conduct a phase 2 clinical trial of atezolizumab (atezo), in patients (pts) with advanced CCS, CS, or dCS (NCT04458922). Methods: We evaluated the effect of targeting PD-L1 with atezo upon the growth and immune landscape of CCS, CS, and dCS. Pts received intravenous atezo 1200 mg/m2 once every 21 days. Prior ICI therapy was not allowed. Tumor biopsy pairs for immuno-pharmacodynamic (IO-PD) studies were collected at baseline and on Cycle 3 Day 1(C3D1); paraffin sections were analyzed using immunofluorescence (IF) microscopy after staining with two multiplexed antibody panels (CD4/FOXP3 and PD-L1/CD8/CD3ζ pY142). Biomarker-positive cells within the tumor area and margins were quantified using image analysis algorithms. Activated cytotoxic T lymphocytes (CTLs) were defined as CD8+ CD3ζ pY142+ and reported as the percentage of the total CD8+ cell density. Results: Nine pts were enrolled per disease cohort. No RECIST objective responses were observed; accrual was closed due to futility. Median progression-free survival (PFS) was 2.66 months (range: 1.3 to 11.7) in CCS, 3.22 (range: 1.4 to 8.9) in CS, and 2.04 (range: 0.4 to 11.7) in dCS. IF microscopy of biopsy pairs from five CCS pts revealed varied immune landscapes: 4/5 C3D1 biopsies contained PD-L1+ cells, 4/5 contained CD8+ cells, and 3/5 contained activated CTLs. Immune phenotype did not generally correlate with response; however, the highest percentage of activated CTLs occurred in the CCS pt with the longest PFS and this pt showed an increase in PD-L1+ cells on treatment—consistent with target engagement of the PD-L1/PD-1 immune checkpoint. dCS biopsy pairs (N=3) also contained a range of biomarker densities that did not correlated with PFS. In dCS and CCS, on-treatment increases in the percentage of activated CTLs were accompanied by increased Treg cell density in some pts. In contrast, CS biopsies (N=5) were uniformly devoid of infiltrating immune cells. Conclusion: The tumor microenvironment of CS is an immune desert, while dCS and CCS tumors contain a range of immune cell compositions. Atezo treatment increased the percentage of activated CTLs and density of PD-L1+ cells in some tumors, but an increase in Treg cells may explain why that pharmacodynamic evidence of ICI activity (the increase in activated CTLs) was not associated with clinical response. Funded NCI Contract No. HHSN261201500003I. Citation Format: Katherine V. Ferry-Galow, Kristin K. Fino, Geraldine O'Sullivan Coyne, Nancy Moore, Elad Sharon, Melissa Burgess, James Chen, Anthony P. Conley, Elizabeth J. Davis, Priscilla Merriam, Albiruni R. Abdul Razak, Brian Van Tine, Jared C. Foster, Naoko Takebe, Christina L. Rosenberger, James H. Doroshow, Alice P. Chen, Ralph E. Parchment. Atezolizumab clinical trial biopsies reveal varied immune landscapes in clear cell sarcoma and chondrosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT263.
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 | 0,001 | 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) | 0,003 | 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 ».