Dataset Information

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 two 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.

SUBMITTER: Gupta S

PROVIDER: S-EPMC8782437 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Gupta Sounak S Vanderbilt Chad M CM Zhang Yanming Y Tickoo Satish K SK Fine Samson W SW Gopalan Anuradha A Chen Ying-Bei YB Sirintrapun Sahussapont J SJ Teo Min Yuen MY Funt Samuel A SA Iyer Gopa G Rosenberg Jonathan E JE Bajorin Dean F DF Bochner Bernard H BH Pietzak Eugene J EJ Ross Dara S DS Ladanyi Marc M Cheville John C JC Solit David B DB Reuter Victor E VE Al-Ahmadie Hikmat A HA

Bladder cancer (Amsterdam, Netherlands) 20211213 4

<h4>Background</h4>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.<h4>Objective</h4>To explore the prevalence of <i>PD-L1</i> copy number alteration in urothelial carcinoma and correlate with response to immune checkpoint inhibitors.<h4>Methods</h4 ...[more]

PMID: 35071713

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