Abstract 1529: Development of lymphoid aggregates in metastatic uveal melanoma tumors treated with tebentafusp
Notice bibliographique
Résumé
Abstract Tebentafusp (tebe), targeting gp100, is the first TCR-CD3 bispecific to demonstrate overall survival (OS) benefit and is approved for the treatment of metastatic uveal melanoma (mUM). We have previously shown B cell recruitment into the tumor associates with OS on tebe [1]. We explored further the formation of lymphoid aggregates (LA) within the tumor microenvironment in response to tebe. HLA-A*02:01+ 2L+ adult patients (pts) with mUM were treated with tebe (NCT02570308). Paired tumor biopsies were collected at baseline (n=70), after 3 doses of tebe (n=48), and at radiographical progression (n=17). Presence of B cells, T cells and macrophages was assessed by immunohistochemistry, using antibodies against CD20, CD3 and CD163 respectively, and digitally quantified. Using digital density analysis, aggregates of ≥10 CD20+ B cells within CD3+ T cell area in a 100µm radius were defined as LA. At progression pts were categorized by OS ≥12 or <12 months. Mean fold change (FC) was used. At baseline, B cells were detected in 90% of pts (median 5 B cells/mm2) with those pts having no more than 2 LA/mm2 (17% pts with 1 LA/mm2 and 3% pts with 2 LA/mm2). The median number of B cells in the biggest LA per sample was 24.B cells were recruited into the tumor after 3 doses of tebe (median 32 B cells/mm2, FC 3, p=6.5e-05). The LA density increased up to 6 LA/mm2 (23% pts with 1 LA/mm2, 8% pts with 2 LA/mm2, 6% pts with 3 LA/mm2 and 2% pts with 6 LA/mm2) with a trend for an increase in LA size (median B cell number in biggest LA = 30, p = 0.67). Tumors with a low baseline CD163+ macrophage to CD3+ T cell ratio, which was previously associated with longer OS on tebe, tended to have more LA/mm2 at baseline and on-treatment than those with a high ratio. At progression, pts with long OS had more B cells in the tumor compared to short OS (median 20 vs 2 B cells/mm2; FC 5, p=0.05). Additionally, more pts with long OS had LA than pts with short OS (6/12 pts vs 1/5 pts respectively) with a density not exceeding 1 LA/mm2. LA size was larger in pts with long OS compared to short OS (median B cell number in biggest LA 30 vs 10 respectively). LA in the short OS patient was found in the normal adjacent tissue compared to the LA in long OS patients which were located in the tumor and invasive margin. Tebe enhanced the formation of LA in the tumor microenvironment, notably in the low immunosuppressed tumors, which is consistent with the hypothesis that it results in epitope spread. These observations provide deeper insight into the mechanism of action of tebe and helps to explain prolonged survival of mUM pts beyond radiographical progression. [1] Greenshields-Watson A. et al., 619, SITC 2022 Citation Format: Takami Sato, Camille Britton-Rivet, Sophie Khakoo, Alistair Easton, Anastasiya Kazachenka, Laura Collins, Emma Leach, Adel Benlarech, Sarah Stanhope, Marcus O. Butler. Development of lymphoid aggregates in metastatic uveal melanoma tumors treated with tebentafusp [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1529.
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 ».