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

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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.

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Abbreviations

BCI:

Bacterial-mediated cancer immunotherapy

Del-1:

Development endothelial locus 1

LFA-1:

Lymphocyte function-associated antigen-1

NETs:

Neutrophil extracellular traps

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Acknowledgements

X. D. L. was supported by the Natural Science Foundation of China (No. 31660733). L. H. P. was supported by the Social Development Foundation of Hainan Province (No. ZDYF2019170).

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Author notes

  1. S. Tian and G. Lin contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, Hainan University, No.58 Renmin Avenue, Haikou, 570228, China

    S. Tian, G. Lin & X. Liu

  2. Hainan Rovincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, No.3 Xueyuan Avenue, Haikou, 57119, China

    L. Piao

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Contributions

SHT and GFL performed experiments and analyzed data. LHP and XDL designed experiments and wrote the manuscript.

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Correspondence to L. Piao or X. Liu.

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All studies in this review have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standard laid down in the 1964 Declaration of Helsinki and its later amendments.

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Tian, S., Lin, G., Piao, L. et al. Del-1 enhances therapeutic efficacy of bacterial cancer immunotherapy by blocking recruitment of tumor-infiltrating neutrophils. Clin Transl Oncol 24, 244–253 (2022). https://doi.org/10.1007/s12094-021-02679-6

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  • DOI: https://doi.org/10.1007/s12094-021-02679-6

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