ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicNatural and Synthetic Immunomodulators in CancerView all 3 articles
Allicin inhibits PD-L1 through the IL-6/JAK2/STAT3 pathway to suppress immune evasion in osteosarcoma
Provisionally accepted
- 1Shandong University of Traditional Chinese Medicine, Jinan, China
- 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Objective: PD-L1 is one of the most critical immune checkpoint proteins, inhibiting T-cell immune responses by binding to PD-1. This study aims to validate that allicin can regulate PD-L1 expression through the IL-6/JAK2/STAT3 pathway, thereby inhibiting immune evasion in osteosarcoma. Methods: We screened differentially expressed genes associated with prognosis using the GEO database and identified the IL-6/JAK2/STAT3/PDL1 pathway through KEGG and GO enrichment analysis. We established the HOS human osteosarcoma cell line and the K7M2 mouse osteosarcoma cell line. Both cell lines were treated with allicin at concentrations of 12.5, 25, and 50 μmol/L. Transwell, clonogenic, and scratch assays validated allicin's inhibitory effects on osteosarcoma cell growth, migration, and invasion. Western Blot assays measured expression levels of key proteins including IL-6, JAK2, STAT3, PD-L1, and phosphorylated JAK2/STAT3. Animal models were established in Balb/c mice and treated with allicin. Mouse clinical signs, tumor volume, and size were recorded. Tumor microenvironment and immune cell infiltration markers (CD3+, CD4+, CD8+, IFN-γ, granzyme B) were analyzed via flow cytometry and immunofluorescence. Immunofluorescence and immunohistochemistry were employed to detect the expression of PD-L1, CD8, and other relevant markers in mouse tumor models, validating allicin's inhibitory effect on immune evasion. Results: In osteosarcoma cell lines treated with allicin, the IL-6/JAK2/STAT3 signaling pathway was downregulated, and PD-L1 expression was significantly suppressed. In allicin-treated mice, recruitment of CD4+ and CD8+ T cells increased, IFN-γ and granzyme B expression enhanced, and tumor immune evasion was markedly inhibited. Conclusion: Allicin suppresses PD-L1 expression by modulating the IL-6/JAK2/STAT3 signaling pathway, thereby improving the tumor microenvironment and inhibiting immune evasion in osteosarcoma cells. This study demonstrates the potential of allicin as an adjunct to immunotherapy.
Keywords: allicin, IL-6/JAK2/STAT3, Immune Evasion, Osteosarcoma, PD-L1
Received: 29 Oct 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 gong, Jin, Cui, Sun, Xie and Zhang. 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:
Wenpeng Xie
Yongkui Zhang
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