Publication Date

8-26-2025

Journal

Cancers

DOI

10.3390/cancers17172780

PMID

40940877

PMCID

PMC12427482

PubMedCentral® Posted Date

8-26-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Osteosarcoma is a type of bone cancer that mostly affects kids and teens. The biggest danger is when the cancer spreads to the lungs, and current treatments do not work well for those cases. Immunotherapy, which helps the body’s immune system fight cancer, has worked for other cancers but is limited for osteosarcoma because we do not fully understand the environment around the tumor. Our research looked at various cells around the tumor to study why patients have worse outcomes. We found that certain cells, called M2 macrophages (M2) and myeloid-derived suppressor cells (MDSC), which weaken the immune system, are very common in these tumors. When there are a lot of these cells, the cancer is more likely to come back. Even worse, when these immune-suppressing cells are very close to M2 in the tumor, the cancer is much more likely to spread to the patient’s lungs. We further showed that M2 helps cancer spread to the lungs in mice. We also discovered that M2 releases a protein called MIP-1α (CCL3), which enhances the ability of cancer cells to spread. These findings could help create new treatments to target these cells and stop the cancer from spreading.

Keywords

osteosarcoma, metastasis, imaging mass cytometry, tumor microenvironment, immunosuppressive cells, spatial analysis, M2 macrophages, immune-tumor crosstalk, MIP-1α, migration

Published Open-Access

yes

nihms-2031306-f0008 (1).jpg (218 kB)
Graphical Abstract

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