Abstract 4693: Characterization of the tumor immune microenvironment in head and neck squamous cell carcinoma (SCCHN)
Notice bibliographique
Résumé
Abstract Approximately 20% of advanced SCCHNs respond to anti-PD-(L)1. We aimed to inform rational combination therapy development, which might have greater efficacy, by understanding the potential immune effects of the oncogenic human papillomavirus (HPV) in SCCHN, and by characterizing potentially targetable immune checkpoints in the tumor microenvironment (TME). Immunohistochemistry (IHC) was performed on archival SCCHN specimens from 27 treatment-naive patients. HPV testing with p16 IHC was confirmed by HPV genotyping. IHC for PD-L1 assessed percentage of positive tumor cells, and whether PD-L1 was expressed in an adaptive or constitutive pattern (i.e., PD-L1+ tumor cells juxtaposed to TILs or in the absence of TILs, respectively). PD-L1 on infiltrating immune cells was scored separately. IHC for CD3, CD4, CD8, CD20, CD68, FoxP3, PD-1, PD-L2, LAG-3, TIM-3, GITR and IDO was quantified using Halo image analysis for density of positive cells. Among 27 SCCHN specimens, 14 were HPV(-) and 13 were HPV+ (one HPV58, 12 HPV16). In 19 of 27 specimens (70%), ≥5% of tumor cells had PD-L1 cell surface expression by IHC, including 9 HPV+ and 10 HPV(-) cases. Among 23 tumors expressing any level of PD-L1 (≥1% tumor cells+), 12 displayed an adaptive PD-L1 expression pattern, 5 a constitutive pattern, and 6 were mixed. All tumors were infiltrated by immune cells (ICs). Notably, 26 of 27 specimens (96%) contained PD-L1+ immune cells (range 5-80% of ICs expressing PD-L1). The proportion of PD-L1+ ICs exceeded PD-L1+ tumor cells in 21/26 (81%) cases. Neither the proportion of PD-L1+ tumor cells nor infiltrating immune cells correlated with tumor viral status. When compared to HPV(-) tumors, HPV+ tumors contained significantly higher densities of CD3+, CD4+, CD8+, CD20+, and PD-1+ cells (p<0.02); there was a trend towards an increased density of FoxP3+ cells in HPV+ tumors. However, when comparing specimens in which tumor cells were PD-L1+ vs. (-), none of these markers were differentially expressed. This may reflect heterogeneous mechanisms driving constitutive vs. adaptive PD-L1 expression patterns in SCCHN. In addition to finding abundant IDO expression in these specimens (>500 IDO+ cells/mm2 in 17/27 specimens), IDO was expressed by tumor cells as well as ICs in 12/27 (44%) cases (range 5-95% tumor cells+). In summary, we found that both HPV+ and (-) SCCHNs abundantly express PD-L1 on tumor and/or stromal cells, although HPV+ tumors are more heavily infiltrated by ICs. Multiple other immune checkpoints are expressed in these tumors, providing options for therapeutic co-targeting. Tumor DNA sequencing is in progress to explore the genetic basis for constitutive vs. adaptive PD-L1 expression. These studies are expected to provide a comprehensive portrait of the SCCHN TME, with implications for future immunotherapy development. Funded by the Bristol-Myers Squibb International Immuno-Oncology Network and NCI R01 CA142779 Citation Format: Farah Succaria, Pia Kvistborg, Elizabeth L. Engle, Tracee L. McMiller, Elizabeth Thompson, Alan E. Berger, John Haanen, Suzanne L. Topalian, Janis M. Taube. Characterization of the tumor immune microenvironment in head and neck squamous cell carcinoma (SCCHN) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4693.
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 | 0,001 | 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 ».