التفاصيل البيبلوغرافية
| العنوان: |
Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden |
| المؤلفون: |
Morrison, Carl, Pabla, Sarabjot, Conroy, Jeffrey M., Nesline, Mary K., Glenn, Sean T., Dressman, Devin, Cruz Merino, Luis de la, Ernstoff, Marc S. |
| المساهمون: |
Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. CTS151: Bioquímica médica. |
| بيانات النشر: |
BMC |
| سنة النشر: |
2024 |
| المجموعة: |
idUS - Deposito de Investigación Universidad de Sevilla |
| مصطلحات موضوعية: |
Pembrolizumab, Nivolumab, Ipilimumab, Algorithmic analysis, Inflamed, Borderline, Immune Desert |
| الوصف: |
Background: Immune checkpoint inhibitors (ICIs) have changed the clinical management of melanoma. However, not all patients respond, and current biomarkers including PD-L1 and mutational burden show incomplete predictive performance. The clinical validity and utility of complex biomarkers have not been studied in melanoma. Methods: Cutaneous metastatic melanoma patients at eight institutions were evaluated for PD-L1 expression, CD8+ T-cell infiltration pattern, mutational burden, and 394 immune transcript expression. PD-L1 IHC and mutational burden were assessed for association with overall survival (OS) in 94 patients treated prior to ICI approval by the FDA (historical-controls), and in 137 patients treated with ICIs. Unsupervised analysis revealed distinct immune clusters with separate response rates. This comprehensive immune profiling data were then integrated to generate a continuous Response Score (RS) based upon response criteria (RECIST v.1.1). RS was developed using a single institution training cohort (n = 48) and subsequently tested in a separate eight institution validation cohort (n = 29) to mimic a real-world clinical scenario. Results: PD-L1 positivity ≥1% correlated with response and OS in ICI-treated patients, but demonstrated limited predictive performance. High mutational burden was associated with response in ICI-treated patients, but not with OS. Comprehensive immune profiling using RS demonstrated higher sensitivity (72.2%) compared to PD-L1 IHC (34.25%) and tumor mutational burden (32.5%), but with similar specificity. Conclusions: In this study, the response score derived from comprehensive immune profiling in a limited melanoma cohort showed improved predictive performance as compared to PD-L1 IHC and tumor mutational burden. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
Journal of Immunotherapy of Cancer, 6 (1), 32.; https://jitc.bmj.com/content/6/1/32Test; https://idus.us.es/handle//11441/156114Test |
| الإتاحة: |
https://idus.us.es/handle//11441/156114Test |
| حقوق: |
Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.497CAAAD |
| قاعدة البيانات: |
BASE |
