Bioengineered Stroma‐Camouflaged Nanovesicles Disrupt the IDO1/CD276 Immunosuppressive Circuit to Reinvigorate Antitumor Immunity
5 affiliations
- 1Key Laboratory of Nanomedical Technology (Education Department of Fujian Province) Department of Pharmaceutical Analysis School of Pharmacy Fujian Medical University Fuzhou China
- 2Department of Urology Harvard Medical School Brigham and Women's Hospital Boston Massachusetts USA
- 3State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen China
- 4Public Technology Service Center Fujian Medical University Fuzhou Fujian China
- 5Core Laboratory Fuzhou Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine Fuzhou Fujian China
Abstract
The cooperative upregulation of IDO1 and the immune checkpoint CD276 in solid tumors establishes a dual immunosuppressive circuit that depletes tryptophan, accumulates kynurenines, and silences T‐cells. We engineered fibroblast‐mimetic nanovesicles (AM@UIO‐BMS/DOX) that uniquely integrate stromal‐camouflaged tumor accumulation, CD276 checkpoint blockade, and co‐delivery of doxorubicin with the clinical IDO1 inhibitor BMS‐986205. The fibroblast‐derived membrane coating promotes accumulation in fibroblast‐rich tumor regions, while surface‐anchored anti‐CD276 scFv enables precision tumor specific targeting and concurrent checkpoint neutralization. Within the tumor microenvironment, doxorubicin elicits immunogenic cell death, and BMS‐986205 metabolically recalibrates the tryptophan–kynurenine equilibrium, relieving the metabolic suppression that otherwise blunts T‐cell priming. In syngeneic tumor models, this bioengineered platform profoundly remodeled the immune microenvironment, as evidenced by a tripartite shift: enhanced dendritic cell maturation and cross‐presentation, expansion of Granzyme B+ cytotoxic CD8+ T lymphocytes, and selective depletion of CD25+FoxP3+ regulatory T cells. This concerted action effectively converted immunologically “cold” tumors into an inflamed phenotype, overcoming intrinsic chemoresistance and adaptive immune evasion. Collectively, our findings establish that bioengineered stroma‐camouflaged nanovesicles disrupt the dual IDO1/CD276 immunosuppressive circuit, enhancing antitumor immunity and offering a promising strategy to surmount chemo‐immunotherapy resistance in advanced solid tumors.
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BibTeX
@article{zhang2026bioengineered,
title = {{Bioengineered Stroma‐Camouflaged Nanovesicles Disrupt the IDO1/CD276 Immunosuppressive Circuit to Reinvigorate Antitumor Immunity}},
author = {Ziqi Zhang and Jing Luo and Mengdi Zhang and Jingying Zhuang and Yating Zheng and Yang Zhang and Zhihong Huang and Xinhua Lin and Shuzhen Xu and Hong Yao and Gang Liu and Bing Chen},
journal = {Advanced Science},
year = {2026},
month = oct,
doi = {10.1002/advs.78142},
url = {https://doi.org/10.1002/advs.78142},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bioengineered Stroma‐Camouflaged Nanovesicles Disrupt the IDO1/CD276 Immunosuppressive Circuit to Reinvigorate Antitumor Immunity
AU - Ziqi Zhang
AU - Jing Luo
AU - Mengdi Zhang
AU - Jingying Zhuang
AU - Yating Zheng
AU - Yang Zhang
AU - Zhihong Huang
AU - Xinhua Lin
AU - Shuzhen Xu
AU - Hong Yao
AU - Gang Liu
AU - Bing Chen
PY - 2026
DA - 2026/10/25
JO - Advanced Science
DO - 10.1002/advs.78142
UR - https://doi.org/10.1002/advs.78142
AB - The cooperative upregulation of IDO1 and the immune checkpoint CD276 in solid tumors establishes a dual immunosuppressive circuit that depletes tryptophan, accumulates kynurenines, and silences T‐cells. We engineered fibroblast‐mimetic nanovesicles (AM@UIO‐BMS/DOX) that uniquely integrate stromal‐camouflaged tumor accumulation, CD276 checkpoint blockade, and co‐delivery of doxorubicin with the clinical IDO1 inhibitor BMS‐986205. The fibroblast‐derived membrane coating promotes accumulation in fibroblast‐rich tumor regions, while surface‐anchored anti‐CD276 scFv enables precision tumor specific targeting and concurrent checkpoint neutralization. Within the tumor microenvironment, doxorubicin elicits immunogenic cell death, and BMS‐986205 metabolically recalibrates the tryptophan–kynurenine equilibrium, relieving the metabolic suppression that otherwise blunts T‐cell priming. In syngeneic tumor models, this bioengineered platform profoundly remodeled the immune microenvironment, as evidenced by a tripartite shift: enhanced dendritic cell maturation and cross‐presentation, expansion of Granzyme B+ cytotoxic CD8+ T lymphocytes, and selective depletion of CD25+FoxP3+ regulatory T cells. This concerted action effectively converted immunologically “cold” tumors into an inflamed phenotype, overcoming intrinsic chemoresistance and adaptive immune evasion. Collectively, our findings establish that bioengineered stroma‐camouflaged nanovesicles disrupt the dual IDO1/CD276 immunosuppressive circuit, enhancing antitumor immunity and offering a promising strategy to surmount chemo‐immunotherapy resistance in advanced solid tumors.
SN - 2198-3844
ER -