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 BernardsIrene L. Andrulis, Marleen Kok, Karin E. de Visser, Marjanka K. Schmidt

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere1509820
JournalOncoImmunology
Volume7
Issue number12
DOIs
StatePublished - Dec 2 2018

Keywords

  • BRCA1-like
  • Breast cancer
  • PD-L1
  • TILs
  • mutations

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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