PD-L1 expression in medulloblastoma: An evaluation by subgroup

Allison 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 Keith Meeker, Eric Raabe, Kenneth J Cohen, Charles G Eberhart, Peter C. Burger, Mariarita Santi, Janis M Taube, Andrew Mark PardollCharles G. Drake, Michael Lim

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)19177-19191
Number of pages15
JournalOncotarget
Volume9
Issue number27
DOIs
StatePublished - Apr 10 2018

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Medulloblastoma
Interferon-gamma
Biomarkers
Cell Line
Tumor Microenvironment
Gamma Rays
Brain Neoplasms
Neoplasms
Radiation
Pediatrics
Cytokines

Keywords

  • B7-H1
  • Brain tumor
  • Medulloblastoma
  • PD-1
  • PD-L1

ASJC Scopus subject areas

  • Oncology

Cite this

Martin, A., Nirschl, C. J., Polanczyk, M. J., Bell, W. R., Nirschl, T. R., Harris-Bookman, S., ... Lim, M. (2018). PD-L1 expression in medulloblastoma: An evaluation by subgroup. Oncotarget, 9(27), 19177-19191. https://doi.org/10.18632/oncotarget.24951

PD-L1 expression in medulloblastoma : An evaluation by subgroup. / Martin, Allison; Nirschl, Christopher J.; Polanczyk, Magda J.; Bell, W. Robert; Nirschl, Thomas R.; Harris-Bookman, Sarah; Phallen, Jillian; Hicks, Jessica; Martinez, Daniel; Ogurtsova, Aleksandra; Xu, Haiying; Sullivan, Lisa M.; Meeker, Alan Keith; Raabe, Eric; Cohen, Kenneth J; Eberhart, Charles G; Burger, Peter C.; Santi, Mariarita; Taube, Janis M; Pardoll, Andrew Mark; Drake, Charles G.; Lim, Michael.

In: Oncotarget, Vol. 9, No. 27, 10.04.2018, p. 19177-19191.

Research output: Contribution to journalArticle

Martin, A, Nirschl, CJ, Polanczyk, MJ, Bell, WR, Nirschl, TR, Harris-Bookman, S, Phallen, J, Hicks, J, Martinez, D, Ogurtsova, A, Xu, H, Sullivan, LM, Meeker, AK, Raabe, E, Cohen, KJ, Eberhart, CG, Burger, PC, Santi, M, Taube, JM, Pardoll, AM, Drake, CG & Lim, M 2018, 'PD-L1 expression in medulloblastoma: An evaluation by subgroup', Oncotarget, vol. 9, no. 27, pp. 19177-19191. https://doi.org/10.18632/oncotarget.24951
Martin A, Nirschl CJ, Polanczyk MJ, Bell WR, Nirschl TR, Harris-Bookman S et al. PD-L1 expression in medulloblastoma: An evaluation by subgroup. Oncotarget. 2018 Apr 10;9(27):19177-19191. https://doi.org/10.18632/oncotarget.24951
Martin, Allison ; Nirschl, Christopher J. ; Polanczyk, Magda J. ; Bell, W. Robert ; Nirschl, Thomas R. ; Harris-Bookman, Sarah ; Phallen, Jillian ; Hicks, Jessica ; Martinez, Daniel ; Ogurtsova, Aleksandra ; Xu, Haiying ; Sullivan, Lisa M. ; Meeker, Alan Keith ; Raabe, Eric ; Cohen, Kenneth J ; Eberhart, Charles G ; Burger, Peter C. ; Santi, Mariarita ; Taube, Janis M ; Pardoll, Andrew Mark ; Drake, Charles G. ; Lim, Michael. / PD-L1 expression in medulloblastoma : An evaluation by subgroup. In: Oncotarget. 2018 ; Vol. 9, No. 27. pp. 19177-19191.
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AU - Nirschl, Christopher J.

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AU - Bell, W. Robert

AU - Nirschl, Thomas R.

AU - Harris-Bookman, Sarah

AU - Phallen, Jillian

AU - Hicks, Jessica

AU - Martinez, Daniel

AU - Ogurtsova, Aleksandra

AU - Xu, Haiying

AU - Sullivan, Lisa M.

AU - Meeker, Alan Keith

AU - Raabe, Eric

AU - Cohen, Kenneth J

AU - Eberhart, Charles G

AU - Burger, Peter C.

AU - Santi, Mariarita

AU - Taube, Janis M

AU - Pardoll, Andrew Mark

AU - Drake, Charles G.

AU - Lim, Michael

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