PD-1 and PD-L1 expression in renal cell carcinoma with sarcomatoid differentiation

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

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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 sarco-matoid 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 sarco-matoid 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.

Original languageEnglish (US)
Pages (from-to)1303-1307
Number of pages5
JournalCancer Immunology Research
Volume3
Issue number12
DOIs
StatePublished - Dec 2015

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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