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

Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues.

Author information

1
Department of Pediatrics, Stanford University, Stanford, California.
2
Bristol-Myers Squibb, Princeton, New Jersey.
3
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
4
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
5
Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland.
6
Department of Pediatric and Adolescent Medicine, Gustave Roussy Institute, Villejuif, France.
7
Department of Medical Biology and Pathology, Gustave Roussy Institute, Villejuif, France.
8
Vancouver Prostate Center, Vancouver, British Columbia, Canada.
9
Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
10
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
11
Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania.

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

PMID:
28608950
DOI:
10.1002/cncr.30724
[Indexed for MEDLINE]
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