An Oral Salmonella-Based Vaccine inhibits liver metastasesby promoting tumor-specific T cell-mediated immunity in celiac and portal lymph nodes. A preclinical study.

VENDREL ALEJANDRINA; MONGINI C; GRAVISACO F; CANELLADA, A; TESSONE A; GOIN J; WALDNER C

Frontiers in Immunology

Frontiers.org

Año: 2016 vol. 7

Primary tumor excision is one of the most widely used therapies of cancer. However,the risk of metastases development still exists following tumor resection. The liver is acommon site of metastatic disease for numerous cancers. Breast cancer is one of themost frequent sources of metastases to the liver. The aim of this work was to evaluate theefficacy of the orally administered Salmonella Typhi vaccine strain CVD 915 on the developmentof liver metastases in a mouse model of breast cancer. To this end, one group ofBALB/c mice was orogastrically immunized with CVD 915, while another received PBS asa control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells intothe spleen and subjected to splenectomy. This oral Salmonella-based vaccine producedan antitumor effect, leading to a decrease in the number and volume of liver metastases.Immunization with Salmonella induced an early cellular immune response in mice. Thisinnate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC)detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac andportal lymph nodes (LDLN) 21 days after oral bacterial inoculation. The antitumor immuneresponse inside the liver was associated with increased CD4+ and dendritic cell populationsas well as with an inflammatory infiltrate located around liver metastatic nodules.Enlarged levels of inflammatory cytokines (IFN-γ and TNF) were also detected in IHIC.Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8+IFN-γ+) were found in the celiac and portal lymph nodes ofSalmonella-treated mice. This study provides first evidence for the involvement of LDLN inthe development of an efficient cellular immune response against hepatic tumors, whichresulted in the elimination of liver metastases after oral Salmonella-based vaccination.