Soluble forms of PD-L1 and PD-1 as prognostic and predictive markers of sunitinib efficacy in patients with metastatic clear cell renal cell carcinoma

Oncoimmunology. 2020 Nov 25;9(1):1846901. doi: 10.1080/2162402X.2020.1846901.

Abstract

Metastatic clear cell renal cell carcinoma (mccRCC) benefits from several treatment options in the first-line setting with VEGFR inhibitors and/or immunotherapy including anti-PD-L1 or anti-PD1 agents. Identification of predictive biomarkers is highly needed to optimize patient care. Circulating markers could reflect the biology of metastatic disease. Therefore, we evaluated soluble forms of PD-L1 (sPD-L1) and PD-1 (sPD-1) in mccRCC patients. The levels of sPD-L1 and sPD-1 were evaluated from plasma samples of mccRCC patients before they received a first-line treatment (T0) by the VEGFR inhibitor sunitinib (50 patients) or by the anti-VEGF bevacizumab (37 patients). The levels of sPD-L1 and sPD-1 were correlated to clinical parameters and progression-free survival (PFS). High levels of sPD-1 or sPDL1 were not correlated to PFS under bevacizumab while they were independent prognostic factors of PFS in the sunitinib group. Patients with high T0 plasmatic levels of sPD-L1 had a shorter PFS (11.3 vs 22.5 months, p = .011) in the sunitinib group. Equivalent shorter PFS was found with high levels of sPD-1 (8.6 vs 14.1 months, p = .009). mccRCC patients with high plasmatic levels of sPD-L1 or sPD-1 are poor responders to sunitinib. sPD-L1 or sPD-1 could be a valuable tool to guide the optimal treatment strategy including VEGFR inhibitor.

Keywords: ccRCC; immune checkpoint inhibitor; plasmatic marker; sPD-1; sPD-L1; soluble PD-1; soluble PD-L1; sunitinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell* / drug therapy
  • Humans
  • Prognosis
  • Programmed Cell Death 1 Receptor*
  • Sunitinib / therapeutic use

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Programmed Cell Death 1 Receptor
  • Sunitinib

Grants and funding

This work was supported by the Canceropole PACA, the Fondation de France, the Ligue Nationale contre le Cancer (Equipe Labellisée 2019), The National Institute of Cancer (INCA, SUNITRES), the National Agency for Research (ANR, TARMAC) and the FX Mora and Flavien Foundations. This study was conducted as part of the Centre Scientifique de Monaco Research Program, funded by the Government of the Principality of Monaco.