CD274 (PD-L1) Copy Number Changes (Gain) & Response to Immune Checkpoint Blockade Therapy in Carcinomas of the Urinary Tract

Sounak Gupta, Chad M. Vanderbilt, Yanming Zhang, Satish K. Tickoo, Samson W. Fine, Anuradha Gopalan, Ying Bei Chen, Sahussapont J. Sirintrapun, Min Yuen Teo, Samuel A. Funt, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, Bernard H. Bochner, Eugene J. Pietzak, Dara S. Ross, Marc Ladanyi, John C. Cheville, David B. Solit, Victor E. ReuterHikmat A. Al-Ahmadie

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)395-400
Number of pages6
JournalBladder Cancer
Issue number4
StatePublished - 2021


  • PD-L1
  • bladder cancer
  • copy number changes
  • immune checkpoint blockade

ASJC Scopus subject areas

  • Oncology
  • Urology


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