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Cited by 197Cancer Immunotherapy and BiomarkersSarcoma Diagnosis and TreatmentImmunotherapy and Immune Responses

Enhanced T-Cell Immunity to Osteosarcoma Through Antibody Blockade of PD-1/PD-L1 Interactions

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Lussier, Danielle M., O’Neill, Lauren, Nieves, Lizbeth M., McAfee, Megan S., Holechek, Susan A., Collins, Andrea W., Dickman, Paul, Jacobsen, Jeffrey +2 more·2015·Journal of Immunotherapy
DOI 10.1097/cji.0000000000000065PMC PMC6426450
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Abstract

Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma. We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy.

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  • Blockade of PD-1/PD-L1 interactions significantly promotes the anti-tumor activity of tumor-infiltrating CTLs in vitro and in vivo.

    “Blockade of PD-1/PD-L1 interactions significantly promotes the anti-tumor activity of tumor-infiltrating CTLs in vitro and in vivo [82].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [82]

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Authors
Lussier, D. M., O’Neill, L., Nieves, L. M., McAfee, M. S., Holechek, S. A., Collins, A. W., Dickman, P., Jacobsen, J., Hingorani, P., & Blattman, J. N.
Affiliations
  • Phoenix Children's Hospital (US)
  • Arizona State University (US)
Corresponding author
  • Lussier, Danielle M.
  • McAfee, Megan S.
  • Blattman, Joseph N.
ORCID
Venue
Journal of Immunotherapy
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-04
Volume
38
Issue
3
Pages
96-106
ISSN
1524-9557 (ISSN-L)
DOI
10.1097/cji.0000000000000065
PMC
PMC6426450
OpenAlex
W2314452004
Cited by
197
References
5
Citations by year
2026: 4 · 2025: 13 · 2024: 11 · 2023: 17 · 2022: 15 · 2021: 19 · 2020: 33 · 2019: 15 · 2018: 17 · 2017: 23 · 2016: 24 · 2015: 6
FWCI
10.19
Type
journal article
Language
en
Open access
Locations
  • Journal of Immunotherapy (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Arizona State University Library Digital Repository (Arizona State University) (submittedVersion)
Funders
National Institute of General Medical Sciences (R25GM071798)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
osteosarcoma, PD-1, PD-L1, T cell immunity, cytotoxic T lymphocytes, immune checkpoint blockade, metastatic osteosarcoma, tumor-infiltrating lymphocytes, tumor immunology
MeSH terms
Adolescent, Adult, Animals, Antibodies, Monoclonal, Bone Neoplasms, Child, Cytotoxicity, Immunologic, Disease Models, Animal, Humans, Neoplasm Metastasis, Prognosis, Osteosarcoma, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Gene Expression, Cytokines, Lymphocytes, Tumor-Infiltrating, Disease Progression, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Young Adult, Immunomodulation, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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