title: Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma.
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.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Pratistha
authors.initials: P
authors.lastname: Koirala
authors.affiliation: Division of Pediatric Hematology, Oncology, Marrow &Blood Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Roth
authors.affiliation: Division of Pediatric Hematology, Oncology, Marrow &Blood Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gill
authors.affiliation: Division of Pediatric Hematology, Oncology, Marrow &Blood Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Sajida
authors.initials: S
authors.lastname: Piperdi
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Chinai
authors.affiliation: Division of Pediatric Hematology, Oncology, Marrow &Blood Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College, Bronx, NY, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Geller
authors.affiliation: Department of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College, Bronx, NY, USA.
authors.forename: Bang H
authors.initials: BH
authors.lastname: Hoang
authors.affiliation: Division of Pediatric Hematology, Oncology, Marrow &Blood Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Park
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.|New York-Presbyterian Morgan Stanley Children's Hospital, Columbia University Medical Center, New York, New York, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fremed
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.|Division of Pediatric Hematology, Oncology, Marrow &Blood Cell Transplantation, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D061986:MCF-7 Cells; D008264:Macrophages / Q000276:immunology; D012516:Osteosarcoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human