Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma
Open accessAbstract
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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A high proportion of osteosarcoma samples have an increased number of tumour-infiltrating lymphocytes, suggesting immune system activation in many patients with osteosarcoma.
“A high proportion of osteosarcoma samples have an increased number of tumour-infiltrating lymphocytes, suggesting immune system activation in many patients with osteosarcoma 180 .”
From Osteosarcoma (2022) · cites this paper as [180]
PDX model systems are valuable in basic science and personalized medicine because they have clinical and molecular features representative of human disease.
“These PDX model systems are of particular value in both basic science and potentially personalized medicine research 180,183,222 as they have clinical and molecular features that are quite representative of the human disease 223,224,225,226 .”
From Osteosarcoma (2022) · cites this paper as [180]
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- Authors
- Koirala, P., Roth, M. E., Gill, J., Piperdi, S., Chinai, J. M., Geller, D. S., Hoang, B. H., Park, A., Fremed, M. A., Zang, X., & Gorlick, R.
- Affiliations
- Albert Einstein College of Medicine (US)
- Morgan Stanley Children's Hospital (US)
- Corresponding author
- Gorlick, Richard
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-07-26
- Volume
- 6
- Issue
- 1
- Pages
- 30093-30093
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4960483
- OpenAlex
- W2491306389
- Cited by
- 267
- References
- 65
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 15 · 2023: 25 · 2022: 30 · 2021: 42 · 2020: 57 · 2019: 30 · 2018: 16 · 2017: 18 · 2016: 5
- FWCI
- 20.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (PC131008)
- Swim Across America
- National Institutes of Health (5k12ca132783-12, 1s10od019961-01)
- National Cancer Institute (K12-CA132783, 1S10OD019961-01, K12 CA-132783-04, R01CA175495)
- National Institute of General Medical Sciences (T32GM007288)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100525)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Keywords
- osteosarcoma, PD-L1 expression, tumor immune microenvironment, immune cell infiltration, prognostic factors, event-free survival, PD-1, dendritic cells, macrophages, natural killer cells, tumor-infiltrating lymphocytes, antigen-presenting cells
- MeSH terms
- Breast Neoplasms, Dendritic Cells, Humans, Killer Cells, Natural, Macrophages, Prognosis, Osteosarcoma, Biomarkers, Tumor, Lymphocytes, Tumor-Infiltrating, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Tumor Microenvironment, B7-H1 Antigen, MCF-7 Cells
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