Engineered Salmonella carrying siRNA-PD-1 shrinks orthotopically implanted bladder cancer in rats.

BACKGROUND

Currently, the application of engineered bacteria in tumour treatment has received increasing attention. It has been proved that Bacillus Calmette-Guerin (BCG) can effectively treat bladder cancer (BC). In addition, immune checkpoint blockade is an effective method for tumour treatment. Programmed cell death protein 1 (PD-1), an important immunosuppressive molecule, binds to programmed death ligand receptor 1 (PD-L1) and inhibits the anti-tumour effects of T cells.

METHODS

The plasmid encoding siRNA-PD-1 was constructed, and the rat BC in situ model was established. After the treatment, morphological changes in tumour tissue were detected by HE staining, and the apoptotic cells in tumour tissue were detected by TUNEL. The expression of related proteins was detected by Western blotting, and the proportion of CD4+ and CD8+ T cells in the spleen was detected by flow cytometry.

RESULTS

We found that the engineered Salmonella significantly inhibited the growth and incidence of tumours and increased the apoptosis of tumours. Importantly, engineered Salmonella carrying siRNA-PD-1 enhanced the anti-tumour immune response by inhibiting PD-1 expression and increased the CD8+ T cell infiltration in tumour tissue, while elevating the ratio of CD8+/CD4+ in spleens.

CONCLUSION

We demonstrated that engineered Salmonella siRNA-PD-1 exerted significant anti-tumour effects on BC.