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Published on: February 8, 2018
CD274 (PD-L1) Copy Number Changes (Gain) & Response to Immune Checkpoint Blockade Therapy in Carcinomas of the
Sounak Gupta1,2, Chad M Vanderbilt1, Yanming Zhang1
1Department of Pathology, Memorial Sloan Kettering Cancer Center.
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.
Insights
Copy number alterations in PD-L1 may predict response to immune checkpoint inhibitors in urothelial carcinoma. Amplification correlated with higher protein expression and clinical benefit, while deletion was associated with progression.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- Immune checkpoint inhibitors (ICIs) are crucial for urothelial carcinoma treatment.
- Durable responses to ICIs are limited to a subset of patients.
- Identifying predictive biomarkers for ICI response is critical.
Purpose of the Study:
- To investigate the prevalence of PD-L1 copy number alterations (CNAs) in urothelial carcinoma.
- To correlate PD-L1 CNAs with response to immune checkpoint inhibitors.
Main Methods:
- Analysis of 1050 urothelial carcinomas using targeted next-generation sequencing.
- Assessment of PD-L1 protein expression and copy number status (NGS/FISH).
- Correlation of genetic findings with detailed treatment response data.
Main Results:
- Identified 9 tumors with PD-L1 amplification and 9 with PD-L1 deletion.
- PD-L1 amplification was associated with highest protein expression.
- Patients with PD-L1 amplified tumors showed higher rates of clinical benefit and durable response to immunotherapy.
Conclusions:
- PD-L1 copy number alterations may serve as potential biomarkers for predicting immunotherapy response in urothelial carcinoma.
- Further validation in larger patient cohorts is warranted.
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