OncoImmunology (Dec 2018)

Assessment of PD-L1 expression across breast cancer molecular subtypes, in relation to mutation rate, BRCA1-like status, tumor-infiltrating immune cells and survival

  • Marcelo Sobral-Leite,
  • Koen Van de Vijver,
  • Magali Michaut,
  • Rianne van der Linden,
  • Gerrit K.J. Hooijer,
  • Hugo M. Horlings,
  • Tesa M. Severson,
  • Anna Marie Mulligan,
  • Nayana Weerasooriya,
  • Joyce Sanders,
  • Annuska M Glas,
  • Diederik Wehkamp,
  • Lorenza Mittempergher,
  • Kelly Kersten,
  • Ashley Cimino-Mathews,
  • Dennis Peters,
  • Erik Hooijberg,
  • Annegien Broeks,
  • Marc J. van de Vijver,
  • Rene Bernards,
  • Irene L. Andrulis,
  • Marleen Kok,
  • Karin E. de Visser,
  • Marjanka K. Schmidt

DOI
https://doi.org/10.1080/2162402X.2018.1509820
Journal volume & issue
Vol. 7, no. 12

Abstract

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To better understand the expression pattern of programmed death-ligand 1 (PD-L1) expression in different breast cancer types, we characterized PD-L1 expression in tumor and tumor-infiltrating immune cells, in relation to mutation rate, BRCA1-like status and survival. We analyzed 410 primary treatment-naive breast tumors comprising 162 estrogen receptor-positive (ER+) and HER2−, 101 HER2+ and 147 triple-negative (TN) cancers. Pathologists quantified tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells and TILs using whole slides and tissue microarray. Mutation rate was assessed by DNA sequencing, BRCA1-like status using multiplex ligation-dependent probe amplification, and immune landscape by multiplex image analyses of CD4, CD68, CD8, FOXP3, cytokeratin, and PD-L1. Half of PD-L1 scores evaluated by tissue microarray were false negatives compared to whole slide evaluations. We observed at least 1% of PD-L1-positive (PD-L1+) cells in 53.1% of ER+HER2−, 73.3% of HER2+, and 84.4% of TN tumors. PD-L1 expression was higher in ductal compared to lobular carcinomas, also within ER+HER2− tumors (p = 0.04). High PD-L1+ TILs score (> 50%) was independently associated with better outcome in TN tumors (HR = 0.27; 95%CI = 0.10–0.69). Within TN tumors, PD-L1 and TIL scores showed a modest but significant positive association with the number of silent mutations, but no association with BRCA1-like status. Multiplex image analyses indicated that PD-L1 is expressed on multiple immune cells (CD68+ macrophages, CD4+, FOXP3+, and CD8+ T cells) in the breast tumor microenvironment, independent of the PD-L1 status of the tumor cells. We found no evidence that levels of PD-L1+ TILs in TN breast cancer are driven by high mutation rate or BRCA1-like status.

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