PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse

Zheng, Bingxin; Ren, Tingting; Huang, Yi; Sun, Kunkun; Wang, Shidong; Bao, Xing; Liu, Kuisheng; Guo, Wei

doi:10.1186/s13045-018-0560-1

Cited by 155Cancer Immunotherapy and BiomarkersSarcoma Diagnosis and TreatmentImmunotherapy and Immune Responses

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PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse

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Zheng, Bingxin, Ren, Tingting, Huang, Yi, Sun, Kunkun, Wang, Shidong, Bao, Xing, Liu, Kuisheng, Guo, Wei·2018·Journal of Hematology & Oncology

DOI 10.1186/s13045-018-0560-1PMC PMC5801803

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Abstract

BACKGROUND: Immune checkpoint inhibitors have led to a breakthrough in solid tumor immunotherapy, but related studies on musculoskeletal tumors are few, especially for PD-L2. METHODS: We examined expression of three molecular effectors of the PD-1 axis in 234 patients with musculoskeletal tumors, including osteosarcoma, chondrosarcoma, synovial sarcoma, and giant cell tumor. Survival analyses and potential mechanisms were investigated in osteosarcoma per the Gene Expression Omnibus (GEO) and immunohistochemistry analyses. In vivo, humanized mice were used to evaluate the effect of nivolumab on osteosarcoma. RESULTS: PD-L1, PD-L2, and PD-1 expression levels were significantly different between the histologic types of the musculoskeletal tumors. For osteosarcoma, PD-L1 was negatively correlated with prognosis, while PD-1 had a negative correlation tendency with overall survival (OS). Meanwhile, PD-L2 had a positive correlation trend with OS. Nivolumab inhibited osteosarcoma metastasis in humanized mice by increasing CD4+ and CD8+ lymphocytes and the cytolytic activity of CD8 lymphocytes in the lung but did not affect primary osteosarcoma growth. CONCLUSION: We systematically detected the expression patterns of PD-L1, PD-L2, and PD-1 in musculoskeletal tumors for the first time and demonstrated the prognostic roles and underlying mechanisms of PD-1 axis in osteosarcoma. Furthermore, PD-1 blockade could effectively control osteosarcoma pulmonary metastasis in vivo. Therefore, the PD-1 axis may be a potential immunotherapeutic target for metastatic osteosarcoma.

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Nivolumab inhibits osteosarcoma metastasis in human PBMC-engrafted mouse models.
“Nivolumab (anti-PD-1 antibody) inhibits osteosarcoma metastasis in human PBMC-engrafted mouse models.”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [83]
Nivolumab promotes tumor lymphocyte infiltration (CD4+ and CD8+ lymphocytes) and enhances the cytolytic activity of CD8 lymphocytes in lung metastases.
“The further study of mechanisms indicated that nivolumab promotes tumor lymphocyte infiltration (CD4+ and CD8+ lymphocytes) and enhances the cytolytic activity of CD8 lymphocytes in lung metastases [83].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [83]

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Additional file 3: Figure S2. of PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse
Zheng, B., Ren, T., Huang, Y., Sun, K., Wang, S., Bao, X., Liu, K., & Guo, W. (2018) · Figshare · doi:10.6084/m9.figshare.5862876
Self-citation
Additional file 2: Figure S1. of PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse
Zheng, B., Ren, T., Huang, Y., Sun, K., Wang, S., Bao, X., Liu, K., & Guo, W. (2018) · Figshare · doi:10.6084/m9.figshare.5862858
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Additional file 1: Table S1. of PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse
Zheng, B., Ren, T., Huang, Y., Sun, K., Wang, S., Bao, X., Liu, K., & Guo, W. (2018) · Figshare · doi:10.6084/m9.figshare.5862837
Self-citation
PD1 and PDL1 expression, tumoral microenvironment (TME) characterization and clinical implication in localized osteosarcoma
Palmerini, E., Agostinelli, C., Picci, P., Pileri, S. A., Lollini, P., Scotlandi, K., Benassi, M. S., & Ferrari, S. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw388.05 · Cited by 2
Clinical outcome of osteosarcoma and its correlation with programmed death-ligand 1 and T cell activation markers
Yoshida, K., Okamoto, M., Sasaki, J., Kuroda, C., Ishida, H., Ueda, K., Okano, S., Ideta, H., Kamanaka, T., Sobajima, A., et al. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s198421 · Cited by 29

Authors: Zheng, B., Ren, T., Huang, Y., Sun, K., Wang, S., Bao, X., Liu, K., & Guo, W.
Affiliations: Peking University People's Hospital (CN)
Corresponding author: Guo, Wei
ORCID: Zheng, Bingxin
Ren, Tingting
Huang, Yi
Sun, Kunkun
Wang, Shidong
Liu, Kuisheng
Guo, Wei
Venue: Journal of Hematology & Oncology
Publisher: Springer Science and Business Media LLC
Published: 2018-02-06
Volume: 11
Issue: 1
Pages: 16-16
ISSN: 1756-8722 (ISSN-L)
DOI: 10.1186/s13045-018-0560-1
PMC: PMC5801803
OpenAlex: W2803454898
Cited by: 151
References: 45
Citations by year: 2026: 9 · 2025: 17 · 2024: 18 · 2023: 19 · 2022: 22 · 2021: 20 · 2020: 29 · 2019: 9 · 2018: 8
FWCI: 6.30
Type: journal article
Language: en
Update notices: correction (2018-03-12)
Open access: gold
doi.org
Licence: cc-by
Locations: Journal of Hematology & Oncology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: National Natural Science Foundation of China (81572633, 81472509)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: PD-L1, PD-L2, nivolumab, osteosarcoma, musculoskeletal tumors, immune checkpoint inhibitors, lung metastasis, humanized mice, CD8+ T cells, prognostic factors, chondrosarcoma, synovial sarcoma, giant cell tumor
MeSH terms: Antineoplastic Agents, Immunological, Nivolumab, Adult, Animals, Bone Neoplasms, Chondrosarcoma, Female, Giant Cell Tumors, Humans, Male, Middle Aged, Neoplasms, Connective Tissue, Osteosarcoma, Sarcoma, Synovial, Cell Line, Tumor, Mice, Young Adult, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Programmed Cell Death 1 Ligand 2 Protein

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PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse

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