Attenuated Salmonella enterica serovar typhimurium carrying the shSTAT3/shPD-L1 recombinant plasmid for colorectal cancer treatment

Abstract

Abstract Colorectal cancer is a malignant tumor of the digestive tract; however, surgical resection and chemoradiotherapy have limited effects, and targeted therapy and immunotherapy have become novel options for prolonging the survival of patients with colorectal cancer. STAT3, a transcription factor, regulates the expression of various proteins and participates in multiple biological processes in tumors, making it a potential target for cancer therapy. PD-L1 are essential immune checkpoint molecules that regulate the tumor microenvironment and immune escape of tumor cells. The increased expression of PD-L1 induce the internal compositional changes of tumor cells, and regulate multiple processes of tumor cell progression. Attenuated Salmonella typhimurium can target tumor tissue to deliver plasmids and preferentially colonize hypoxic areas within the tumor, helping mount an anti-tumor immune response. Therefore, we constructed a double-interfering plasmid shSTAT3/shPD-L1 to reduce the expression of STAT3 and PD-L1 simultaneously and used attenuated Salmonella enterica serovar typhimurium carrying the plasmid to improve tumor tissue targeting and anti-tumor immune effects to explore the anti-tumor effects of double-interfering RNA at multiple levels in vivo and in vitro and to demonstrate its potential application in the clinical treatment of colorectal cancer.