Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps

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Standard

Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps. / Chen, Duo; Li, Qiaxuan; Liang, Hongxin; Huang, Luyu; Zhou, Haiyu; Zheng, Xiang; Wang, Zheng.

In: Biochemical and Biophysical Research Communications, Vol. 619, 2022, p. 97-103.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chen, D, Li, Q, Liang, H, Huang, L, Zhou, H, Zheng, X & Wang, Z 2022, 'Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps', Biochemical and Biophysical Research Communications, vol. 619, pp. 97-103. https://doi.org/10.1016/j.bbrc.2022.06.052

APA

Chen, D., Li, Q., Liang, H., Huang, L., Zhou, H., Zheng, X., & Wang, Z. (2022). Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps. Biochemical and Biophysical Research Communications, 619, 97-103. https://doi.org/10.1016/j.bbrc.2022.06.052

Vancouver

Chen D, Li Q, Liang H, Huang L, Zhou H, Zheng X et al. Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps. Biochemical and Biophysical Research Communications. 2022;619:97-103. https://doi.org/10.1016/j.bbrc.2022.06.052

Author

Chen, Duo ; Li, Qiaxuan ; Liang, Hongxin ; Huang, Luyu ; Zhou, Haiyu ; Zheng, Xiang ; Wang, Zheng. / Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps. In: Biochemical and Biophysical Research Communications. 2022 ; Vol. 619. pp. 97-103.

Bibtex

@article{1b06962b4a1d4f3486c57d01cd10e769,
title = "Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps",
abstract = "Neutrophil extracellular traps (NETs) are extracellular webs of DNA, histones, and granular contents, such as myeloperoxidase (MPO) and elastase, which are released by neutrophils. Reactive oxygen species (ROS) are involved in NETs formation that promote tumor progress. Exenatide could downregulate ROS production in some cell types. However, it is unknown whether Exenatide could influence tumor progress through NETs. Here, we constructed the LLC-based lung cancer and MC38-based colon cancer models and found that Exenatide treatment decreased tumor infiltrated NETs and peripheral MPO-DNA complex and elastase. In addition, the in vitro study showed that Exenatide decreased NETs formation and release. Furthermore, flow cytometry analysis showed that Exenatide treatment reduced ROS production in tumor infiltrated and in vitro neutrophils. However, the ROS inhibitor DPI counteracted the decease of tumor infiltrated and in vitro NETs formation and release by Exenatide. Functionally, the Exenatide/αPD-1 combination therapy was superior to single therapy in restricting tumor growth. Removement of NETs by DNase I weaken the enhancement of αPD-1 treatment by Exenatide. The enriched tumor infiltrated, spleen and lymph node CD8+ T cells from combination therapy group secreted higher concentration of IFN-γ than single treatment. In addition, Exenatide exhibited no direct influence on IFN-γ secretion while purified NETs decreased IFN-γ secretion by CD8+ T cells. The rechallenge study showed that the combination therapy activated long-term tumor rejection. In summary, our findings suggested that Exenatide might be a promising therapeutic candidate for enhancing PD-1 blockade in tumor treatment.",
keywords = "Colon cancer, Exenatide, Lung cancer, Neutrophil extracellular traps, PD-1, Reactive oxygen species",
author = "Duo Chen and Qiaxuan Li and Hongxin Liang and Luyu Huang and Haiyu Zhou and Xiang Zheng and Zheng Wang",
note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
doi = "10.1016/j.bbrc.2022.06.052",
language = "English",
volume = "619",
pages = "97--103",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Exenatide enhanced the antitumor efficacy on PD-1 blockade by the attenuation of neutrophil extracellular traps

AU - Chen, Duo

AU - Li, Qiaxuan

AU - Liang, Hongxin

AU - Huang, Luyu

AU - Zhou, Haiyu

AU - Zheng, Xiang

AU - Wang, Zheng

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022

Y1 - 2022

N2 - Neutrophil extracellular traps (NETs) are extracellular webs of DNA, histones, and granular contents, such as myeloperoxidase (MPO) and elastase, which are released by neutrophils. Reactive oxygen species (ROS) are involved in NETs formation that promote tumor progress. Exenatide could downregulate ROS production in some cell types. However, it is unknown whether Exenatide could influence tumor progress through NETs. Here, we constructed the LLC-based lung cancer and MC38-based colon cancer models and found that Exenatide treatment decreased tumor infiltrated NETs and peripheral MPO-DNA complex and elastase. In addition, the in vitro study showed that Exenatide decreased NETs formation and release. Furthermore, flow cytometry analysis showed that Exenatide treatment reduced ROS production in tumor infiltrated and in vitro neutrophils. However, the ROS inhibitor DPI counteracted the decease of tumor infiltrated and in vitro NETs formation and release by Exenatide. Functionally, the Exenatide/αPD-1 combination therapy was superior to single therapy in restricting tumor growth. Removement of NETs by DNase I weaken the enhancement of αPD-1 treatment by Exenatide. The enriched tumor infiltrated, spleen and lymph node CD8+ T cells from combination therapy group secreted higher concentration of IFN-γ than single treatment. In addition, Exenatide exhibited no direct influence on IFN-γ secretion while purified NETs decreased IFN-γ secretion by CD8+ T cells. The rechallenge study showed that the combination therapy activated long-term tumor rejection. In summary, our findings suggested that Exenatide might be a promising therapeutic candidate for enhancing PD-1 blockade in tumor treatment.

AB - Neutrophil extracellular traps (NETs) are extracellular webs of DNA, histones, and granular contents, such as myeloperoxidase (MPO) and elastase, which are released by neutrophils. Reactive oxygen species (ROS) are involved in NETs formation that promote tumor progress. Exenatide could downregulate ROS production in some cell types. However, it is unknown whether Exenatide could influence tumor progress through NETs. Here, we constructed the LLC-based lung cancer and MC38-based colon cancer models and found that Exenatide treatment decreased tumor infiltrated NETs and peripheral MPO-DNA complex and elastase. In addition, the in vitro study showed that Exenatide decreased NETs formation and release. Furthermore, flow cytometry analysis showed that Exenatide treatment reduced ROS production in tumor infiltrated and in vitro neutrophils. However, the ROS inhibitor DPI counteracted the decease of tumor infiltrated and in vitro NETs formation and release by Exenatide. Functionally, the Exenatide/αPD-1 combination therapy was superior to single therapy in restricting tumor growth. Removement of NETs by DNase I weaken the enhancement of αPD-1 treatment by Exenatide. The enriched tumor infiltrated, spleen and lymph node CD8+ T cells from combination therapy group secreted higher concentration of IFN-γ than single treatment. In addition, Exenatide exhibited no direct influence on IFN-γ secretion while purified NETs decreased IFN-γ secretion by CD8+ T cells. The rechallenge study showed that the combination therapy activated long-term tumor rejection. In summary, our findings suggested that Exenatide might be a promising therapeutic candidate for enhancing PD-1 blockade in tumor treatment.

KW - Colon cancer

KW - Exenatide

KW - Lung cancer

KW - Neutrophil extracellular traps

KW - PD-1

KW - Reactive oxygen species

U2 - 10.1016/j.bbrc.2022.06.052

DO - 10.1016/j.bbrc.2022.06.052

M3 - Journal article

C2 - 35751916

AN - SCOPUS:85132538712

VL - 619

SP - 97

EP - 103

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

ER -

ID: 312697178