Wang and Chen et al. designed an oral, metabolically engineered bacterial platform (EHC) based on the probiotic E. coli strain Nissle 1917 that selectively targeted CRC cells and induced ferroptosis via depletion of intratumoral cysteine and glutathione, thus enhancing immunogenic cell death and remodeling the immunosuppressive TIME. In vivo, oral EHC suppressed orthotopic CRC tumor growth, inhibited metastatic progression, and synergized with anti-PD-1. Immune profiling revealed robust systemic and gut mucosal activation, increased numbers of mature dendritic cells, CD4+ and CD8+ T cells, and pro-inflammatory macrophages.
Contributed by Katherine Turner
(1) Wang L (2) Chen Y (3) Shang Y (4) Liu J (5) Zhao M (6) Jin L (7) Shi Y (8) Zhang R (9) Chen Z (10) Yin T (11) Qiao C (12) Wang Z
Wang and Chen et al. designed an oral, metabolically engineered bacterial platform (EHC) based on the probiotic E. coli strain Nissle 1917 that selectively targeted CRC cells and induced ferroptosis via depletion of intratumoral cysteine and glutathione, thus enhancing immunogenic cell death and remodeling the immunosuppressive TIME. In vivo, oral EHC suppressed orthotopic CRC tumor growth, inhibited metastatic progression, and synergized with anti-PD-1. Immune profiling revealed robust systemic and gut mucosal activation, increased numbers of mature dendritic cells, CD4+ and CD8+ T cells, and pro-inflammatory macrophages.
Contributed by Katherine Turner
ABSTRACT: Immunotherapy for colorectal cancer (CRC) remains limited due to the inherently low tumor immunogenicity and the profoundly immunosuppressive tumor microenvironment (TME). Herein, capitalizing on the metabolic traits and anatomical accessibility of CRC, we propose a broadly applicable oral strategy based on metabolically engineered bacteria (EcN-HlpA-CGL [EHC]) for CRC immunotherapy. Mechanistically, cystathionine γ-lyase expressed by EHC disrupts redox homeostasis, triggering ferroptosis in CRC cells and thereby enhancing tumor immunogenicity. Concurrently, the intrinsic adjuvant activity of the bacteria amplifies the cancer-immunity cycle driven by immunogenic cell death and remodels the immunosuppressive TME. In vivo studies demonstrate that this orally delivered engineered bacterial platform not only suppresses the growth of orthotopic CRC tumors but also inhibits metastatic progression, indicating the induction of a potent systemic immune response. Immune profiling confirms robust systemic and gut mucosal immune activation following oral administration. Collectively, this oral metabolically engineered bacterial platform is precisely tailored to the features of CRC and offers a safe and effective immunotherapeutic strategy for this malignancy.
Author Info:
(1) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (2) Engineer
ing Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. Electronic address: chenyang@xidian.edu.cn. (3) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (4) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (5) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (6) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (7) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (8) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. (9) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. Electronic address: chenzhuang@xidian.edu.cn. (10) Research Center of Nano Technology and Application Engineering, The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan 523808, P.R. China. Electronic address: wsyt132@163.com. (11) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. Electronic address: qiaochaoqiang@xidian.edu.cn. (12) Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, P.R. China. Electronic address: wangzl@xidian.edu.cn.
Citation: Cell Rep Med 2026 Oct 12 103111 Epub10/12/2026
