title: PD-1 and PD-L1 Expression in Renal Cell Carcinoma with Sarcomatoid Differentiation.
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.
authors: Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida.
authors: Richard W
authors: RW
authors: Joseph
authors: Caris Life Sciences, Phoenix, Arizona.
authors: Sherri Z
authors: SZ
authors: Millis
authors: Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona.
authors: Estrella M
authors: EM
authors: Carballido
authors: Caris Life Sciences, Phoenix, Arizona.
authors: David
authors: D
authors: Bryant
authors: Caris Life Sciences, Phoenix, Arizona.
authors: Zoran
authors: Z
authors: Gatalica
authors: Caris Life Sciences, Phoenix, Arizona.
authors: Sandeep
authors: S
authors: Reddy
authors: Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona.
authors: Alan H
authors: AH
authors: Bryce
authors: U.S. Oncology/Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada.
authors: Nicholas J
authors: NJ
authors: Vogelzang
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona.
authors: Melissa L
authors: ML
authors: Stanton
authors: Department of Urology, Mayo Clinic Hospital, Phoenix, Arizona.
authors: Erik P
authors: EP
authors: Castle
authors: Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona. ho.thai@mayo.edu.
authors: Thai H
authors: TH
authors: Ho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor