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PD-1 and PD-L1 Expression in Renal Cell Carcinoma with Sarcomatoid Differentiation
Richard W Joseph1, Sherri Z Millis2, Estrella M Carballido3
1Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida.
Abstract:
Monoclonal antibodies that target the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) axis have antitumor activity against multiple cancers. The presence of sarcomatoid differentiation in renal cell carcinoma (RCC) is associated with resistance to targeted therapy and poor responses to IL2 immunotherapy. Given the aggressive nature of RCC with sarcomatoid differentiation and the exclusion of sarcomatoid histology from metastatic RCC clinical trials, less is understood regarding selection of therapies. Here, we characterized the PD-1/PD-L1 axis in RCC with sarcomatoid differentiation. We directly compared two PD-L1 antibodies and found concordance of PD-L1 positivity in 89% of tested RCCs with sarcomatoid differentiation. Coexpression of PD-L1 on neoplastic cells and the presence of PD-1-positive tumor-infiltrating lymphocytes were identified in 50% (13 of 26) of RCCs with sarcomatoid differentiation. In contrast, only 1 of 29 clear cell RCCs (3%) had concurrent expression of PD-L1 and PD-1 (P = 0.002). Our study suggests that RCC with sarcomatoid differentiation may express PD-1/PD-L1 at a higher percentage than RCC without sarcomatoid differentiation, and patients with these tumors may be good candidates for treatment with anti-PD-1/PD-L1 therapies.
Insights
Renal cell carcinoma (RCC) with sarcomatoid differentiation shows higher programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) expression. This suggests patients with these aggressive tumors may benefit from anti-PD-1/PD-L1 therapies.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Monoclonal antibodies targeting the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) axis demonstrate antitumor effects in various cancers.
- Sarcomatoid differentiation in renal cell carcinoma (RCC) is linked to resistance to targeted therapies and poor responses to IL2 immunotherapy.
- Limited understanding exists regarding optimal therapies for aggressive RCC with sarcomatoid differentiation due to its exclusion from clinical trials.
Purpose of the Study:
- To characterize the PD-1/PD-L1 axis in RCC with sarcomatoid differentiation.
- To compare the expression of PD-L1 using two different antibodies.
- To assess the potential of anti-PD-1/PD-L1 therapies for this RCC subtype.
Main Methods:
- Direct comparison of two PD-L1 antibodies for positivity in RCC with sarcomatoid differentiation.
- Assessment of PD-L1 coexpression on neoplastic cells and PD-1-positive tumor-infiltrating lymphocytes.
- Comparison of PD-1/PD-L1 expression in RCC with sarcomatoid differentiation versus clear cell RCC.
Main Results:
- High concordance (89%) for PD-L1 positivity was observed between two antibodies in RCC with sarcomatoid differentiation.
- PD-L1 and PD-1 coexpression was found in 50% of RCCs with sarcomatoid differentiation.
- Concurrent PD-L1 and PD-1 expression was significantly higher in sarcomatoid RCC (50%) compared to clear cell RCC (3%, P = 0.002).
Conclusions:
- RCC with sarcomatoid differentiation exhibits a higher prevalence of PD-1/PD-L1 axis expression compared to RCC without this feature.
- Patients with RCC and sarcomatoid differentiation may represent a promising population for anti-PD-1/PD-L1 immunotherapy.
- Further investigation into anti-PD-1/PD-L1 therapies is warranted for this aggressive RCC subtype.
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