Assessment of Programmed Death-Ligand 1 Expression and Tumor-Associated Immune Cells in Pediatric Cancer Tissues

Cancer. 2017 Oct 1;123(19):3807-3815. doi: 10.1002/cncr.30724. Epub 2017 Jun 13.

Abstract

Background: Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers.

Methods: Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression.

Results: Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P < .001).

Conclusions: A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017;123:3807-3815. © 2017 American Cancer Society.

Keywords: checkpoint; immunotherapy; neuroblastoma; pediatric cancer; programmed death 1/programmed death 1 ligand (PD-1/PD-L1) blockade; tumor-infiltrating lymphocytes.

MeSH terms

  • B7-H1 Antigen / analysis*
  • Bone Neoplasms / chemistry
  • Bone Neoplasms / immunology
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Burkitt Lymphoma / chemistry
  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / pathology
  • Child
  • Glioblastoma / chemistry
  • Glioblastoma / immunology
  • Glioblastoma / pathology
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating*
  • Macrophages*
  • Neoplasm Proteins / analysis*
  • Neoplasms / chemistry*
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neuroblastoma / chemistry
  • Neuroblastoma / immunology
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology
  • Osteosarcoma / chemistry
  • Osteosarcoma / immunology
  • Osteosarcoma / pathology
  • Rhabdomyosarcoma / chemistry
  • Rhabdomyosarcoma / immunology
  • Rhabdomyosarcoma / pathology
  • Sarcoma, Ewing / chemistry
  • Sarcoma, Ewing / immunology
  • Sarcoma, Ewing / pathology
  • Tissue Array Analysis

Substances

  • B7-H1 Antigen
  • Neoplasm Proteins