Document Type
Article
Publication Date
6-24-2025
Original Citation
Taylor A,
Sheng J,
Ng P,
Harder JM,
Kumar P,
Ahn J,
Cao Y,
Dzis A,
Jillette NL,
Goodspeed A,
Bodlak A,
Wu Q,
Isakoff M,
George J,
Grassmann J,
Luo D,
Flynn W,
Courtois E,
Robson P,
Hayashi M,
Paolillo A,
Petrilli A,
Caminada de Toledo S,
Balarezo F,
Lindsay A,
Hoang B,
Wong S,
Lau C.
Immunosuppressive Tumor Microenvironment of Osteosarcoma. Cancers (Basel). 2025;17(13):2117
Keywords
JGM, JMG, SS1
JAX Source
Cancers (Basel). 2025;17(13):2117
ISSN
2072-6694
PMID
40647416
DOI
https://doi.org/10.3390/cancers17132117
Grant
This work was funded by CapoStrong Fund and the FAPESP (São Paulo Research Foun- dation) grant number 19/18670–9. Shared services were partially supported in part by the JAX Cancer Center (P30 CA034196). The research was also supported by The Jackson Laboratory CATch program, the Strawbridge Cancer Therapeutic Fund, the T. T. & W.F. Chao Foundation, and the John S Dunn Research Foundation
Abstract
Background/Objectives: Osteosarcoma is the most common malignant bone tumor in children, characterized by a high degree of genomic instability, resulting in copy number alterations and genomic rearrangements without disease-defining recurrent mutations. Clinical trials based on molecular characterization have failed to find new effective therapies or improve outcomes over the last 40 years. Methods: To better understand the immune microenvironment of osteosarcoma, we performed single-cell RNA sequencing on six tumor biopsy samples, combined with a previously published cohort of six samples. Additional osteosarcoma samples were profiled using spatial transcriptomics for the validation of discovered subtypes and to add spatial context. Results: Analysis revealed immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs), regulatory and exhausted T cells, and LAMP3+ dendritic cells. Conclusions: Using cell–cell communication modeling, we identified robust interactions between MDSCs and other cells, leading to NF-κB upregulation and an immunosuppressive microenvironment, as well as interactions involving regulatory T cells and osteosarcoma cells that promoted tumor progression and a proangiogenic niche.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.