Del-1 enhances therapeutic efficacy of bacterial cancer immunotherapy by blocking recruitment of tumor-infiltrating neutrophils.

Abstract

BACKGROUND:

Bacterial-mediated cancer immunotherapy (BCI) elicits a more robust initial immune response than conventional 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.

• Authors: S Tian, G Lin, L Piao, X Liu
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 24 Issue 2 Pg. 244-253 (Feb 2022) ISSN: 1699-3055 [Electronic] Italy
• PMID: 34236615 (Publication Type: Journal Article)
• Copyright: © 2021. Federación de Sociedades Españolas de Oncología (FESEO).

Chemical References

• Calcium-Binding Proteins
• Cell Adhesion Molecules
• Edil3 protein, mouse

Topics

• Animals
• Biological Therapy (methods)
• Calcium-Binding Proteins (physiology)
• Cell Adhesion Molecules (physiology)
• Colonic Neoplasms (immunology, therapy)
• Disease Models, Animal
• Male
• Mice
• Mice, Inbred BALB C
• Neutrophil Infiltration
• Salmonella typhimurium
• Treatment Outcome