Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma

Pratistha Koirala, Michael E. Roth, Jonathan Gill, Sajida Piperdi, Jordan M. Chinai, David S. Geller, Bang H. Hoang, Amy Park, Michael A. Fremed, Xingxing Zang, Richard Gorlick

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Abstract

Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.

Original languageEnglish (US)
Article number30093
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 26 2016

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Tumor Microenvironment
Osteosarcoma
Ligands
Disease-Free Survival
Dendritic Cells
Immunohistochemistry
Tumor-Infiltrating Lymphocytes
Survival
Antigen-Presenting Cells
Natural Killer Cells
Real-Time Polymerase Chain Reaction
Neoplasms
Western Blotting
Macrophages
T-Lymphocytes

ASJC Scopus subject areas

  • General

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Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. / Koirala, Pratistha; Roth, Michael E.; Gill, Jonathan; Piperdi, Sajida; Chinai, Jordan M.; Geller, David S.; Hoang, Bang H.; Park, Amy; Fremed, Michael A.; Zang, Xingxing; Gorlick, Richard.

In: Scientific Reports, Vol. 6, 30093, 26.07.2016.

Research output: Contribution to journalArticle

Koirala, Pratistha ; Roth, Michael E. ; Gill, Jonathan ; Piperdi, Sajida ; Chinai, Jordan M. ; Geller, David S. ; Hoang, Bang H. ; Park, Amy ; Fremed, Michael A. ; Zang, Xingxing ; Gorlick, Richard. / Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. In: Scientific Reports. 2016 ; Vol. 6.
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abstract = "Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25{\%} of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7{\%} vs 47.2{\%}, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3{\%} vs. 83.9{\%}, p = 0.001) and macrophages (45.5{\%} vs. 84.4{\%}, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0{\%}. vs. 69.4{\%}, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.",
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