Evidence map›Paper›PMID 41835111›Full record

ArticleJournal of inflammation research2026

CCL5-Mediated Immune Interactions Drive Osteosarcoma Progression: Insights from Mendelian Randomization, Single-Cell Analysis, and Functional Validation.

Jihao Chen, Yinyan Shao, Junhua Guo, Keke Hu, Xuefei Yang, Ting Huang, Heran Zhou

Abstract read
In one paragraph

Article in Journal of inflammation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jihao Chen *Department of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.
Yinyan Shao *Department of General Medicine, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.
Junhua GuoDepartment of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.
Keke HuDepartment of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.
Xuefei YangDepartment of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.
Ting HuangDepartment of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.
Heran ZhouDepartment of Oncology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, People's Republic of China.ORCID 0009-0002-2519-2654

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Osteosarcoma is a highly aggressive bone malignancy with a complex immune microenvironment. Chronic inflammation and immune cell dysregulation are known to contribute to tumor progression, yet the causal relationships remain largely unclear. Methods: This study integrated Mendelian Randomization (MR), single-cell RNA sequencing (scRNA-seq), bulk transcriptomic analysis, and functional experiments to explore the role of inflammatory cytokines and immune cells in osteosarcoma. MR analyses were performed to identify cytokines and immune cell traits causally related to osteosarcoma risk, followed by scRNA-seq to profile CCL5 expression across cell types. Immune cell infiltration and its association with CCL5 expression were analyzed using the TARGET dataset. Functional assays including qPCR, CCK-8, EdU, and colony formation validated the biological effects of CCL5. Results: MR identified CCL5 as a pro-tumorigenic cytokine with a significant causal association with osteosarcoma (OR > 15). scRNA-seq revealed that monocytes/macrophages and fibroblasts were major CCL5-producing cells. Four immune traits were causally linked to osteosarcoma, including CD86 expression on monocytes and CD127 expression on CD4+ T cells (risk factors), and CD8dim T cell and terminally differentiated CD4+ T cell counts (protective factors). CCL5 expression positively correlated with infiltration of CD8+ T cells, Tregs, and M1 macrophages, and was associated with advanced tumor stage. Co-culture assays confirmed that tumor-associated macrophages with high CCL5 expression enhanced osteosarcoma cell proliferation and colony formation. Conclusion: CCL5 plays a central role in shaping the immune landscape of osteosarcoma and promoting tumor progression. Its spatial association with immune markers such as CD127 and CD86 further supports its regulatory role. These findings provide mechanistic insights and highlight CCL5 as a promising biomarker and immunotherapeutic target in osteosarcoma.

Indexed as

CCL5cytokinesimmune cellsmacrophageosteosarcoma

Identifiers

PMID41835111
PMCPMC12988466

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.