Oncotarget

Research Papers:

PD-L1 expression in medulloblastoma: an evaluation by subgroup

Allison M. Martin _, Christopher J. Nirschl, Magda J. Polanczyk, W. Robert Bell, Thomas R. Nirschl, Sarah Harris-Bookman, Jillian Phallen, Jessica Hicks, Daniel Martinez, Aleksandra Ogurtsova, Haiying Xu, Lisa M. Sullivan, Alan K. Meeker, Eric H. Raabe, Kenneth J. Cohen, Charles G. Eberhart, Peter C. Burger, Mariarita Santi, Janis M. Taube, Drew M. Pardoll, Charles G. Drake and Michael Lim

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Oncotarget. 2018; 9:19177-19191. https://doi.org/10.18632/oncotarget.24951

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Abstract

Allison M. Martin1, Christopher J. Nirschl2, Magda J. Polanczyk1, W Robert Bell3, Thomas R. Nirschl4, Sarah Harris-Bookman5, Jillian Phallen6, Jessica Hicks7, Daniel Martinez8, Aleksandra Ogurtsova9, Haiying Xu9, Lisa M. Sullivan10, Alan K. Meeker7, Eric H. Raabe1,11, Kenneth J. Cohen1, Charles G. Eberhart11, Peter C. Burger11, Mariarita Santi8, Janis M. Taube9, Drew M. Pardoll2, Charles G. Drake12 and Michael Lim13

1Johns Hopkins School of Medicine, Sidney Kimmel Cancer Center, Division of Pediatric Oncology, Baltimore, MD, USA

2Johns Hopkins School of Medicine, Sidney Kimmel Cancer Center, Division of Cancer Immunology, Baltimore, MD, USA

3Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA

4Johns Hopkins School of Medicine, Department of Pathobiology, Baltimore, MD, USA

5Johns Hopkins School of Medicine, Department of Ophthalmology, Baltimore, MD, USA

6Johns Hopkins School of Medicine, Sidney Kimmel Cancer Center, Division of Cancer Biology, Baltimore, MD, USA

7Johns Hopkins School of Medicine, Department of Pathology, Division of Kidney and Urologic Pathology, Baltimore, MD, USA

8Children’s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA

9Johns Hopkins School of Medicine, Department of Dermatology, Division of Dermatologic Pathology and Oral Pathology, Baltimore, MD, USA

10In Jackson, MS, USA

11Johns Hopkins School of Medicine, Department of Pathology, Division of Neuropathology, Baltimore, MD, USA

12Columbia University Medical Center, Division of Hematology/Oncology, New York, NY, USA

13Johns Hopkins School of Medicine, Department of Neurosurgery, Division of Neurosurgical Oncology, Baltimore, MD, USA

Correspondence to:

Allison M. Martin, email: amarti65@jhmi.edu

Keywords: medulloblastoma; PD-1; brain tumor; PD-L1; B7-H1

Received: August 03, 2017     Accepted: March 13, 2018     Published: April 10, 2018

ABSTRACT

Background: This study evaluated the expression of PD-L1 and markers of immune mediated resistance in human medulloblastoma (MB), the most common malignant pediatric brain tumor.

Results: Overall levels of PD-L1 in human MB were low; however, some cases demonstrated robust focal expression associated with increased immune infiltrates. The case with highest PD-L1 expression was a sonic hedgehog (SHH) MB. In cell lines, SHH MB, which are low-MYC expressing, demonstrated both constitutive and inducible expression of PD-L1 while those in Group 3/4 that expressed high levels of MYC had only inducible expression. In vitro, IFN-γ robustly stimulated the expression of PD-L1 in all cell lines while radiation induced variable expression. Forced high MYC expression did not significantly alter PD-L1.

Methods: Human MB tumor samples were evaluated for expression of PD-L1 and immune cell markers in relation to molecular subgroup assignment. PD-L1 expression was functionally analyzed under conditions of interferon gamma (IFN-γ), radiation, and MYC overexpression.

Conclusions: MB expresses low levels of PD-L1 facilitating immune escape. Importantly, TH1 cytokine stimulation appears to be the most potent inducer of PD-L1 expression in vitro suggesting that an inflamed tumor microenvironment is necessary for PD-1 pathway activation in this tumor.


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