Evidence map›Paper›PMID 40592739›Full record

ArticleJournal for immunotherapy of cancer2025

Enhanced antitumor immunity of VNP20009-CCL2-CXCL9 via the cGAS/STING axis in osteosarcoma lung metastasis.

Ruixuan Liu, Qi Liu, Yuming Wang, Tianyi Liu, Zhusheng Zhang, Chong Zhao, Haipeng Tao, Elizabeth Ogando-Rivas, Paul Castillo, Weibin Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–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

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. AttenuatedFrontiers in immunology · 2026
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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

10 authors.

Ruixuan Liu *Orthopedics, Ruijin Hospital, Shanghai, Shanghai, China.ORCID http://orcid.org/0000-0002-8739-3905
Qi Liu *Orthopedics, Ruijin Hospital, Shanghai, Shanghai, China.ORCID http://orcid.org/0000-0002-5684-7396
Yuming Wang *Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, China.
Tianyi LiuNeurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Zhusheng ZhangOrthopedics, Ruijin Hospital, Shanghai, Shanghai, China.
Chong ZhaoNeurosurgery, University of Florida, Gainesville, Florida, USA.
Haipeng TaoNeurosurgery, University of Florida, Gainesville, Florida, USA.
Elizabeth Ogando-RivasNeurosurgery, University of Florida, Gainesville, Florida, USA.
Paul CastilloPediatrics, University of Florida, Gainesville, Florida, USA.
Weibin ZhangOrthopedics, Ruijin Hospital, Shanghai, Shanghai, China zwb10368@rjh.com.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOsteosarcoma (OS) with pulmonary metastasis remains challenging due to limited treatment options and the immunosuppressive nature of the tumor microenvironment (TME). Bacteria-mediated cancer therapy has emerged as a promising strategy for solid tumors but often suffers from limited efficacy due to the immunosuppressive TME, which restricts the intensity and durability of the antitumor immune response. To overcome these challenges, we engineered a novel Salmonella strain, VNP20009-CCL2-CXCL9 (VNP-C-C), leveraging the intrinsic tumor tropism of

methodsVNP-C-C was genetically engineered through electroporation of Plac-CCL2-CXCL9 plasmid and validated in vitro. Its antitumor efficacy, immune regulation capacity and immunomodulatory mechanisms were evaluated in vitro by using OS cell lines and immune cells (dendritic cells (DCs) and macrophages (Mφs)) and in vivo by using both immunocompromised and immunocompetent mouse models of OS lung metastasis.

resultsVNP-C-C effectively accumulated within tumors, triggering immunogenic cell death and subsequently activating the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, thereby robustly promoting type I interferon secretion. The chemokines CCL2 and CXCL9 amplified the immune response by recruiting DCs, Mφs, and T cells to the TME. This orchestrated immune modulation reprogrammed tumor-associated macrophages to an antitumor phenotype, induced DCs maturation, significantly increased T-cell infiltration and activation within tumors, and promoted systemic T-cell memory formation in peripheral lymphoid organs. These effects collectively inhibited OS lung metastasis progression and provided survival benefits in mouse models.

conclusionThe engineered bacterial strain VNP-C-C effectively converts the OS lung metastatic TME into a pro-inflammatory milieu, thereby stimulating robust innate and adaptive immune responses. This offers a highly promising therapeutic avenue for OS lung metastasis with considerable translational potential in cancer immunotherapy.

Indexed as

Bone NeoplasmsChemokine CCL2Chemokine CXCL9Lung NeoplasmsMembrane ProteinsNucleotidyltransferasesOsteosarcomaAnimalsCell Line, TumorCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseFemaleHumansMiceSTING ProteinTumor MicroenvironmentcGAS protein, mouseChemokine CCL2Chemokine CXCL9Cyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMembrane ProteinsNucleotidyltransferasesSting1 protein, mouseSTING ProteinBone CancerImmune modulatoryImmunotherapySolid tumorTumor microenvironment - TME

Identifiers

PMID40592739
PMCPMC12215138

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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 OpenQuestion graph.