CRISPR-engineered probiotics for targeted production of inosine as an immunomodulatory metabolite to enhance cancer immunotherapy response: A review

Background: Cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), has improved cancer survival but remains limited by variable response and adverse effects. Emerging evidence demonstrated that gut microbiome, particularly inosine, is a critical determinant of immunotherapy efficacy through its capacity to produce immunomodulatory metabolites that enhance T-cell activation, promote dendritic cell function, and restore anti-tumor immunity. Advances in CRISPR-Cas technology has enabled precise engineering of probiotic strains for targeted inosine production, offering a potentially safer and more effective immunomodulatory approach. Purpose: This study aims to evaluate CRISPR-engineered probiotics for targeted production of inosine as an immunomodulatory metabolite to enhance cancer immunotherapy response. Method: A narrative literature review was conducted using secondary data collected from online databases such as PubMed, ScienceDirect, and ResearchGate. Results: A total of 11 studies were analyzed, showing that CRISPR-engineered probiotics can precisely enhance inosine production via targeted purine metabolic pathways. Microbiota-derived inosine promotes T-cell and dendritic cell activation through A2A receptor signaling, driving Th1 polarization, IFN-γ secretion, CD8+ cytotoxic T-cell activity, and supporting T-cell metabolism under stress. Engineered probiotics demonstrated more consistent inosine production and predictable immunomodulatory effects compared to conventional strains, potentially synergizing with ICIs to reduce tumor growth and improve antitumor immunity. Conclusion: CRISPR-engineered probiotics for targeted production of inosine suggest potential to enhance cancer immunotherapy response.