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PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases
L B Jilaveanu1, B Shuch2, C R Zito3
11. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Background:
Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response.
Patients And Methods:
A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative immunofluorescence. Assessment of intra- and inter-tumor heterogeneity and primary and metastatic tumor expression was performed using a method of Automated Quantitative Analysis (AQUA).
Results:
The median AQUA scores were higher in metastatic than primary specimens (P < 0.0001). The correlation between PD-L1 expression in matched primary and metastatic specimens was weak (R= 0.24). Within a given tumor, variable PD-L1 staining heterogeneity was seen, however the degree of heterogeneity was similar in primary and metastatic sites (P = 0.482).
Conclusions:
The weak correlation between PD-L1 expression in primary and metastatic sites for a given patient suggests that expression in nephrectomy specimens cannot be used to select metastatic RCC patients for PD-L1 and PD-1 inhibitors. The intra-tumor heterogeneity seen in both primary and metastatic specimens indicates that a single core biopsy might not be sufficient to determine PD-L1 expression.
Insights
Programmed death ligand (PD-L1) expression differs between primary and metastatic renal cell carcinoma (RCC). Tumor PD-L1 levels in nephrectomy specimens may not predict response to PD-1/PD-L1 inhibitors in metastatic RCC patients.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Programmed death ligand (PD-L1) facilitates immune escape in renal cell carcinoma (RCC).
- PD-L1 expression levels may predict patient response to PD-1/PD-L1 inhibitor therapies.
- Targeting PD-L1 is a promising strategy in RCC treatment.
Purpose of the Study:
- To assess PD-L1 expression in primary and metastatic clear cell RCC.
- To evaluate the correlation of PD-L1 expression between matched primary and metastatic tumors.
- To investigate PD-L1 expression heterogeneity within RCC tumors.
Main Methods:
- Utilized a tissue microarray (TMA) with four biopsy cores from 34 matched primary and metastatic clear cell RCC pairs.
- Quantified PD-L1 expression using quantitative immunofluorescence and Automated Quantitative Analysis (AQUA).
- Assessed intra- and inter-tumor heterogeneity and expression differences between primary and metastatic sites.
Main Results:
- Metastatic RCC specimens showed significantly higher PD-L1 expression than primary specimens (median AQUA scores, P < 0.0001).
- A weak correlation (R=0.24) was observed between PD-L1 expression in matched primary and metastatic tumors.
- Significant intra-tumor heterogeneity of PD-L1 staining was present in both primary and metastatic sites, with similar degrees of heterogeneity (P = 0.482).
Conclusions:
- PD-L1 expression in primary RCC (nephrectomy) specimens is a poor predictor of expression in metastatic sites.
- Reliance on nephrectomy PD-L1 levels for selecting metastatic RCC patients for PD-1/PD-L1 inhibitors is not recommended.
- Intra-tumor heterogeneity suggests that single core biopsies may be insufficient for accurate PD-L1 assessment.
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