Resumen de Del‑1 enhances therapeutic efficacy of bacterial cancer immunotherapy by blocking recruitment of tumor‑infiltrating neutrophils

S. Tian, G. Lin, L. Piao, X. Liu

• Background Bacterial-mediated cancer immunotherapy (BCI) elicits a more robust initial immune response than conven- tional immunotherapy, but does not prevent tumor recurrence and metastasis. BCI is associated with recruitment of tumor- infiltrating neutrophils, which could suppress the therapeutic efficacy of this modality. Development endothelial locus 1 (Del-1), a potent inhibitor of neutrophil recruitment, antagonizes lymphocyte function-associated antigen-1 on the vascular endothelium. Here, we aimed to determine the effect of Del-1-secreting S.t△ppGpp on anti-tumor activity and tumor- infiltrating neutrophil recruitment in a mouse model of colon cancer.

  Methods We investigated the anti-cancer activity of Del-1-secreting engineered Salmonella (△ppGpp S. Typhimurium) in the mice colon cancer models.

  Results In the present study, we identified that Del-1-secreting engineered Salmonella had more potent anti-cancer activity compared with normal S.t△ppGpp without Del-1 secretion. We postulated that Del-1 expression increased M1 macrophage recruitment to tumors by decreasing tumor-infiltrating neutrophils. This approach could enhance the anti-cancer effects of S.t△ppGpp.

  Conclusions Collectively, the approach of using engineered bacteria that deliver Del-1 to block tumor-infiltrating neutrophil recruitment is a potential therapeutic approach.