Targeted tumor desialylation by engineered probiotic reprograms the tumor microenvironment to potentiate immunotherapy
- 1Sun Yat-sen University
Abstract
Tumor hypersialylation drives immunosuppression and limits immunotherapy efficacy by shielding tumor cells and engaging inhibitory immune receptors. Here, we engineered Escherichia coli Nissle 1917 (EcN{Delta}pgi-SAS) as a metabolically confined "desialylation catalyst" to remodel the tumor microenvironment. This strain combines HER2-directed adhesion, hypoxia-inducible surface sialidase display for targeted glycan cleavage, and sialic acid catabolism to prevent glycolytic recycling. Critically, disrupting glucose metabolism ({Delta}pgi) restricts bacterial proliferation to sialic acid-rich tumor microenvironment, significantly enhancing biosafety. In mice, EcN{Delta}pgi-SAS colonized tumors and effectively desialylated tumor cells, synergizing with anti-PD-L1 to suppress growth of immunologically "cold" tumors. Mechanistically, desialylation reversed immunosuppression by broadly enhancing antitumor immunity. Orally administered EcN{Delta}pgi-SAS substantially inhibited colorectal carcinogenesis, repaired epithelial barrier integrity by restoring tight junctions, and prevented adenoma formation. This integrated strategy establishes a clinically translatable platform for reversing immunosuppression in solid tumors.
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BibTeX
@misc{wang2026targeted,
title = {{Targeted tumor desialylation by engineered probiotic reprograms the tumor microenvironment to potentiate immunotherapy}},
author = {J. Wang and J. Wang and T. OuYang and B. Shi and H. Meng and Z.-W. Mao and W. Xia},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.756258},
url = {https://www.biorxiv.org/content/10.64898/2026.10.04.756258v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Targeted tumor desialylation by engineered probiotic reprograms the tumor microenvironment to potentiate immunotherapy
AU - J. Wang
AU - J. Wang
AU - T. OuYang
AU - B. Shi
AU - H. Meng
AU - Z.-W. Mao
AU - W. Xia
PY - 2026
DA - 2026/10/04
PB - bioRxiv
DO - 10.64898/2026.10.04.756258
UR - https://www.biorxiv.org/content/10.64898/2026.10.04.756258v1
AB - Tumor hypersialylation drives immunosuppression and limits immunotherapy efficacy by shielding tumor cells and engaging inhibitory immune receptors. Here, we engineered Escherichia coli Nissle 1917 (EcN{Delta}pgi-SAS) as a metabolically confined "desialylation catalyst" to remodel the tumor microenvironment. This strain combines HER2-directed adhesion, hypoxia-inducible surface sialidase display for targeted glycan cleavage, and sialic acid catabolism to prevent glycolytic recycling. Critically, disrupting glucose metabolism ({Delta}pgi) restricts bacterial proliferation to sialic acid-rich tumor microenvironment, significantly enhancing biosafety. In mice, EcN{Delta}pgi-SAS colonized tumors and effectively desialylated tumor cells, synergizing with anti-PD-L1 to suppress growth of immunologically "cold" tumors. Mechanistically, desialylation reversed immunosuppression by broadly enhancing antitumor immunity. Orally administered EcN{Delta}pgi-SAS substantially inhibited colorectal carcinogenesis, repaired epithelial barrier integrity by restoring tight junctions, and prevented adenoma formation. This integrated strategy establishes a clinically translatable platform for reversing immunosuppression in solid tumors.
ER -