Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non‐small‐cell lung cancer characterizes the features of response to PD‐1 blockade plus chemotherapy
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Résumé
BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy. METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group. CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 découle