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 interleukin-2 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 2 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 was identified in 50% (13/26) 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=.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.
Cancer immunology research 2015 Aug 25 [Epub ahead of print]
Richard W Joseph, Sherri Z Millis, Estrella M Carballido, David Bryant, Zoran Gatalica, Sandeep Reddy, Alan H Bryce, Nicholas J Vogelzang, Melissa L Stanton, Erik P Castle, Thai H Ho
Division of Hematology and Medical Oncology, Mayo Clinic , Medical Affairs, Caris Life Sciences , Division of Hematology and Medical Oncology, Mayo Clinic , N/A, Caris Life Sciences , N/A, Caris Life Sciences , N/A, Caris Life Sciences , Division of Hematology and Medical Oncology, Mayo Clinic , Medical Oncology, US Oncology/Comprehensive Cancer Centers of Nevada , Laboratory Medicine/Pathology, Mayo Clinic , Urology, Mayo Clinic Hospital , Division of Hematology and Medical Oncology, Mayo Clinic Ho