ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1686854
Transcriptomic Analysis Reveals TME-Mediated Macrophage IFIT1 Upregulation and CX3CR1 Suppression Drive Osteosarcoma Progression
Provisionally accepted
- First Affiliated Hospital, Guangxi Medical University, Nanning, China
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Introduction: Osteosarcoma (OS) is one of the most common bone tumors which prognosis of patients is unsatisfactory. Due to the stagnancy in conventional treatments, researchers begin to find therapeutic targets from tumor microenvironment (TME) and tumor associated macrophages (TAM). We aim to investigate the influence of the effects of OS TME on gene expression of macrophages which may provide reference to OS treatment. Methods: RNA sequencing was performed on BMMs cultured with or without K7M2 CM for 48 hours to analyze gene expression changes. Utilize single-cell sequencing and PCR to examine the expression levels of IFIT1 and CX3CR1. Verify their functions through flow cytometry, cloning, wound healing, and transwell assays using IFIT1 protein and CX3CR1 inhibitors. Results: We observed changes in the morphology and transcriptome of K7M2 CM exposed BMMs. The differential expressed genes (DEGs) have complex interactions with each other and are enriched to multiple functions and pathways. The upregulation of IFIT1 and the downregulation of CX3CR1 are the most representative. Inhibiting CX3CR1 can promote TAM polarization, thereby accelerating the progression of osteosarcoma. Additionally, increasing IFIT1 also promotes osteosarcoma. Conclusions: Stimulation of OS TME could change the gene expression of macrophages. Our data offer the cellular and molecular reference for future investigate therapeutic targets of OS.
Keywords: Osteosarcoma microenvironment, Tumor-associated macrophages, transcriptome analysis, IFIT1, CX3CR1
Received: 28 Aug 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Wang, He, Liang, Su, Zhao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jinmin Zhao, zhaojinmin@126.com
Qian Liu, liuqian@gxmu.edu.cn
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