Engineered Gut Bacteria Enhances Immune Response in Colorectal Cancer Models

Researchers have engineered a strain of gut-targeting bacteria that triggers immune responses in colorectal cancer models, according to a study published in Science Translational Medicine. The bacterial therapy was found to promote the development of mature immune structures within tumors, improving survival outcomes in preclinical models.

Colorectal cancer (CRC) is the second leading cause of cancer-related death globally. For patients with advanced disease, treatment options remain limited. Immunotherapy, which recruits the body’s immune system to attack cancer cells, has shown promise, but many tumors develop ways to evade immune detection.

To address this, researchers from the Yong Loo Lin School of Medicine at the National University of Singapore and Central South University in China genetically modified a strain of Salmonella typhimurium to colonize tumor tissue and release a therapeutic protein known as LIGHT. This protein activates a key immune pathway, helping to reverse the tumor’s immunosuppressive environment.

Local delivery of therapeutic proteins stimulates immune structures

The engineered bacteria were shown to induce the formation of mature tertiary lymphoid structures (mTLSs) within colorectal tumors. These structures act as local immune ‘hubs’, providing a site for immune cells to coordinate a response against cancer cells.

The bacteria released the LIGHT protein directly into the tumor environment, stimulating a specific immune signaling pathway – LIGHT-HVEM – and activating group 3 innate lymphoid cells. This helped initiate a T cell–driven immune response, a mechanism that plays a key role in antitumor immunity.

Reduced tumor burden and improved survival in vivo

In laboratory models, the bacterial therapy led to a reduction in tumor size and extended survival. The treatment was well tolerated and showed no accumulation in healthy organs, suggesting good biocompatibility. Additionally, the therapy was found to help restore gut microbiota composition disrupted by cancer progression.

The study demonstrates how engineered microbes can be used to reshape the tumor microenvironment, a strategy that may complement existing immunotherapies. However, the research is still in the preclinical phase, and further testing is needed to evaluate safety and efficacy in humans.

Reference: Mi Z, Chen J, Zhang Z, et al. Synthetic biology–driven induction of mature TLS formation enhances antitumor immunity in colorectal cancer. Sci Transl Med. 2025. doi:10.1126/scitranslmed.ado8395

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