The association of genomic lesions and PD-1/PD-L1 expression in resected triple-negative breast cancers

  • Michael Barrett (Creator)
  • Elizabeth Lenkiewicz (Creator)
  • Smriti Malasi (Creator)
  • Anamika Basu (Creator)
  • Jennifer H. Yearley (Creator)
  • Lakshmanan Annamalai (Contributor)
  • Ann E. McCullough (Creator)
  • Heidi E. Kosiorek (Creator)
  • Pooja Narang (Creator)
  • Melissa Wilson (Contributor)
  • Meixuan Chen (Contributor)
  • Karen Anderson (Creator)
  • Barbara A. Pockaj (Creator)
  • Ann E. McCullough (Creator)



Abstract Background Elevated PD-L1 expression on tumor cells, a context associated with an adaptive immune response, has been linked to the total burden of copy number variants (CNVs) in aneuploid tumors, to microsatellite instability (MSI), and to specific genomic driver lesions, including loss of PTEN, MYC amplification, and activating mutations in driver oncogenes such as KRAS and PIK3CA. Triple-negative breast cancers (TNBCs) typically have high levels of CNVs and diverse driver lesions in their genomes. Thus, there is significant interest in exploiting genomic data to develop predictive immunotherapy biomarkers for patients with TNBC. Methods Whole tissue samples from 55 resected TNBCs were screened by immunohistochemistry (IHC) for PD-1 and PD-L1 by using validated antibodies and established scoring methods for staining of tumor and non-tumor cells. In parallel, we interrogated biopsies from each resection with DNA content flow cytometry and sorted the nuclei of diploid, tetraploid, and aneuploid cell populations. CNVs were mapped with CNV oligonucleotide arrays by using purified (>95%) tumor populations. We generated whole exome data for 12 sorted tumor samples to increase the resolution within loci of interest and to incorporate somatic mutations into our genomic signatures. Results and Conclusions PD-L1 staining was detected on tumor cells in 29 out of 54 (54%) evaluable cases and was associated with increased overall survival (P = 0.0024). High levels of PD-1 and PD-L1 (IHC ≥4) were present in 11 out of 54 (20%) and 20 out of 54 (37%) cases with staining of PD-L1 primarily on tumor cells for 17 out of 20 (85%) cases. The latter included tumors with both high (>50) and low (
Date made available2018

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