CD274 (PD-L1) copy number changes (gain) & response to immune checkpoint blockade therapy in carcinomas of the urinary tract Journal Article
| Authors: | Gupta, S.; Vanderbilt, C. M.; Zhang, Y.; Tickoo, S. K.; Fine, S. W.; Gopalan, A.; Chen, Y. B.; Sirintrapun, S. J.; Teo, M. Y.; Funt, S. A.; Iyer, G.; Rosenberg, J. E.; Bajorin, D. F.; Bochner, B. H.; Pietzak, E. J.; Ross, D. S.; Ladanyi, M.; Cheville, J. C.; Solit, D. B.; Reuter, V. E.; Al-Ahmadie, H. A. |
| Article Title: | CD274 (PD-L1) copy number changes (gain) & response to immune checkpoint blockade therapy in carcinomas of the urinary tract |
| Abstract: | BACKGROUND: Immune checkpoint inhibitors are an important therapeutic option for urothelial carcinoma, but durable responses are achieved in a minority of patients. Identifying pre-treatment biomarkers that may predict response to these therapies or who exhibit intrinsic resistance, is of paramount importance. OBJECTIVE: To explore the prevalence of PD-L1 copy number alteration in urothelial carcinoma and correlate with response to immune checkpoint inhibitors. METHODS: We analyzed a cohort of 1050 carcinomas of the bladder and upper urinary tract that underwent targeted next generation sequencing, prospectively. We assessed PD-L1 protein expression, copy number status (next generation sequencing/FISH), and detailed treatment response. RESULTS: We identified 9 tumors with PD-L1 amplification and 9 tumors with PD-L1 deletion. PD-L1 protein expression was the highest in PD-L1 amplified tumors. Of the 9 patients whose tumors harbored PD-L1 amplification, 6 received immunotherapy with 4 deriving clinical benefit, and 2 achieving durable response. Of the 9 patients whose tumors had PD-L1 copy number losses, 4 received immunotherapy with 3 experiencing disease progression. CONCLUSIONS: PD-L1 copy number alterations may serve as potential biomarkers of response to immunotherapy in urothelial carcinoma patients, if validated in larger cohorts. © 2021 - IOS Press. All rights reserved. |
| Keywords: | bladder cancer; pd-l1; immune checkpoint blockade; copy number changes |
| Journal Title: | Bladder Cancer |
| Volume: | 7 |
| Issue: | 4 |
| ISSN: | 2352-3727 |
| Publisher: | IOS Press |
| Date Published: | 2021-01-01 |
| Start Page: | 395 |
| End Page: | 400 |
| Language: | English |
| DOI: | 10.3233/blc-201532 |
| PROVIDER: | scopus |
| PMCID: | PMC8782437 |
| PUBMED: | 35071713 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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