Reversal of the neutrophil barrier for potentiating immune-engineered bacteria therapy in pancreatic cancer
4 affiliations
- 1MOE Key Laboratory for Biomedical Photonics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
- 2Department of Oncology, Huanggang Central Hospital Affiliated to Hubei University of Science and Technology, No.126 Qi’an Road, Huanggang 438000, China
- 3Hubei Clinical Medical Research Center of Esophageal and Gastric Malignancy, Huanggang 438021, China
- 4Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Abstract
Engineered bacterial therapy holds the potential to overcome drug delivery barriers; remodel the immunosuppressive tumor microenvironment; and enable precise, sustained drug release within tumors. However, after infiltrating the tumor, engineered bacteria extensively recruit neutrophils, which directly phagocytose and eliminate the bacteria, confining them to the necrotic core and impeding their migration toward proliferative tumor regions, thereby limiting therapeutic efficacy. In this study, we introduce indole-3-acetic acid as an adjuvant to bacterial therapy. Note that, indole-3-acetic acid directly suppresses neutrophil recruitment. Simultaneously, it synergizes with gemcitabine to eliminate existing neutrophils. Experiments demonstrate that this method promotes intratumoral colonization, enhances immune activation efficiency, and can significantly reduce the clearance of therapeutic bacteria in pancreatic cancer mouse models. Taking PD-L1 antibody-expressing engineered bacteria as an example, the combination further strengthens T-cell-mediated antitumor immune responses through synergistic immune checkpoint blockade, ultimately achieving remarkable tumor growth suppression.
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BibTeX
@article{guan2026reversal,
title = {{Reversal of the neutrophil barrier for potentiating immune-engineered bacteria therapy in pancreatic cancer}},
author = {Meng Guan and Xiao-Ting Xie and Bin Zhang and Zi-Hui Yan and Xin-Yue Xu and Jia-Hua Zou and Yuan-Di Zhao and Kai Cheng and Jin-Xuan Fan},
journal = {Cell Reports Medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xcrm.2026.103082},
url = {https://doi.org/10.1016/j.xcrm.2026.103082},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Reversal of the neutrophil barrier for potentiating immune-engineered bacteria therapy in pancreatic cancer
AU - Meng Guan
AU - Xiao-Ting Xie
AU - Bin Zhang
AU - Zi-Hui Yan
AU - Xin-Yue Xu
AU - Jia-Hua Zou
AU - Yuan-Di Zhao
AU - Kai Cheng
AU - Jin-Xuan Fan
PY - 2026
DA - 2026/09/29
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.103082
UR - https://doi.org/10.1016/j.xcrm.2026.103082
AB - Engineered bacterial therapy holds the potential to overcome drug delivery barriers; remodel the immunosuppressive tumor microenvironment; and enable precise, sustained drug release within tumors. However, after infiltrating the tumor, engineered bacteria extensively recruit neutrophils, which directly phagocytose and eliminate the bacteria, confining them to the necrotic core and impeding their migration toward proliferative tumor regions, thereby limiting therapeutic efficacy. In this study, we introduce indole-3-acetic acid as an adjuvant to bacterial therapy. Note that, indole-3-acetic acid directly suppresses neutrophil recruitment. Simultaneously, it synergizes with gemcitabine to eliminate existing neutrophils. Experiments demonstrate that this method promotes intratumoral colonization, enhances immune activation efficiency, and can significantly reduce the clearance of therapeutic bacteria in pancreatic cancer mouse models. Taking PD-L1 antibody-expressing engineered bacteria as an example, the combination further strengthens T-cell-mediated antitumor immune responses through synergistic immune checkpoint blockade, ultimately achieving remarkable tumor growth suppression.
SN - 2666-3791
ER -