Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 2;10(7):1668.
doi: 10.3390/cells10071668.

The Immune Landscape of Osteosarcoma: Implications for Prognosis and Treatment Response

Caterina Cascini  1 , Claudia Chiodoni  1
Affiliations
Review

The Immune Landscape of Osteosarcoma: Implications for Prognosis and Treatment Response

Caterina Cascini et al. Cells. .

Abstract

Osteosarcoma (OS) is a high-grade malignant stromal tumor composed of mesenchymal cells producing osteoid and immature bone, with a peak of incidence in the second decade of life. Hence, although relatively rare, the social impact of this neoplasm is particularly relevant. Differently from carcinomas, molecular genetics and the role of the tumor microenvironment in the development and progression of OS are mainly unknown. Indeed, while the tumor microenvironment has been widely studied in other solid tumor types and its contribution to tumor progression has been definitely established, tumor-stroma interaction in OS has been quite neglected for years. Only recently have new insights been gained, also thanks to the availability of new technologies and bioinformatics tools. A better understanding of the cross-talk between the bone microenvironment, including immune and stromal cells, and OS will be key not only for a deeper knowledge of osteosarcoma pathophysiology, but also for the development of novel therapeutic strategies. In this review, we summarize the current knowledge about the tumor microenvironment in OS, mainly focusing on immune cells, discussing their role and implication for disease prognosis and treatment response.

Keywords: bone marrow; macrophages; mesenchymal stem cells; osteoclasts; osteosarcoma; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The complex osteosarcoma microenvironment in the bone tissue. Osteosarcoma (OS) develops in the highly specialized bone marrow (BM) environment, a highly dynamic tissue composed of bone cells, immune cells, and stromal and vascular cells, embedded in a mineralized extracellular matrix. The different cell types are reciprocally regulated, with OS cells producing factors that recruit and re-program immune, stromal, and bone cells to their advantage, and vice versa, with immune cells, osteoclasts, and stromal cells releasing pro-tumoral molecules such as VEGF (vascular endothelial growth factor), TGFβ (transforming growth factor beta), and IL-6 (interleukin-6). The cross-talk between OS cells and other BM cells may also occur through the release of extracellular vesicles (EVs). OS cells, osteosarcoma cells; MSCs, mesenchymal stem cells; EMT, epithelial-to-mesenchymal transition; G-MDSC, granulocytic myeloid-derived suppressor cells; M-MDSC, monocytic myeloid-derived suppressor cells. Red line: negative signal; green arrow: positive signal.
See this image and copyright information in PMC

References

    1. Mirabello L., Troisi R.J., Savage S.A. Osteosarcoma Incidence and Survival Rates from 1973 to 2004 Data from the Surveillance, Epidemiology, and End Results Program. Cancer. 2009;115:1531–1543. doi: 10.1002/cncr.24121. - DOI - PMC - PubMed
    1. Ta H., Dass C., Choong P., Dunstan D. Osteosarcoma treatment: State of the art. Cancer Metast. Rev. 2009;28:247–263. doi: 10.1007/s10555-009-9186-7. - DOI - PubMed
    1. Gaspar N., Occean B.V., Pacquement H., Bompas E., Bouvier C., Brisse H.J., Castex M.P., Cheurfa N., Corradini N., Delaye J., et al. Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study. Eur. J. Cancer. 2018;88:57–66. doi: 10.1016/j.ejca.2017.09.036. - DOI - PubMed
    1. Mutsaers A.J., Walkley C.R. Cells of origin in osteosarcoma: Mesenchymal stem cells or osteoblast committed cells? Bone. 2014;62:56–63. doi: 10.1016/j.bone.2014.02.003. - DOI - PubMed
    1. Kuijjer M.L., Rydbeck H., Kresse S.H., Buddingh E.P., Roelofs H., Burger H., Myklebost O., Hogendoorn P.C.W., Meza-Zepeda L.A., Cleton-Jansen A.M. Identification of osteosarcoma driver genes by integrative analysis of copy number and gene expression data. Cancer Res. 2012;72 doi: 10.1002/gcc.21956. - DOI - PubMed

Publication types

MeSH terms