Dataset Information

Norepinephrine inhibits CD8⁺ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.

ABSTRACT:

Background

Mental stress-induced neurotransmitters can affect the immune system in various ways. Therefore, a better understanding of the role of neurotransmitters in the tumour immune microenvironment is expected to promote the development of novel anti-tumour therapies.

Methods

In this study, we analysed the plasma levels of neurotransmitters in anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb)-resistance patients and sensitive patients, to identify significantly different neurotransmitters. Subsequently, animal experiments and experiments in vitro were used to reveal the specific mechanism of norepinephrine's (NE) effect on immunotherapy.

Results

The plasma NE levels were higher in anti-PD-1 mAb-resistance patients, which may be the main cause of anti-PD-1 mAb resistance. Then, from the perspective of the immunosuppressive microenvironment to explore the specific mechanism of NE-induced anti-PD-1 mAb resistance, we found that NE can affect the secretion of C-X-C Motif Chemokine Ligand 9 (CXCL9) and adenosine (ADO) in tumour cells, thereby inhibiting chemotaxis and function of CD8⁺ T cells. Notably, the WNT7A/β-catenin signalling pathway plays a crucial role in this progression.

Conclusion

NE can affect the secretion of CXCL9 and ADO in tumour cells, thereby inhibiting chemotaxis and the function of CD8⁺ T cells and inducing anti-PD-1 mAb resistance in lung adenocarcinoma (LUAD).

SUBMITTER: Geng Q

PROVIDER: S-EPMC10050078 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Norepinephrine inhibits CD8<sup>+</sup> T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.

Geng Qishun Q Li Lifeng L Shen Zhibo Z Zheng Yuanyuan Y Wang Longhao L Xue Ruyue R Xue Wenhua W Peng Mengle M Zhao Jie J

British journal of cancer 20230116 7

<h4>Background</h4>Mental stress-induced neurotransmitters can affect the immune system in various ways. Therefore, a better understanding of the role of neurotransmitters in the tumour immune microenvironment is expected to promote the development of novel anti-tumour therapies.<h4>Methods</h4>In this study, we analysed the plasma levels of neurotransmitters in anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb)-resistance patients and sensitive patients, to identify significa ...[more]

PMID: 36646807

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Project description:Background: Prostate cancer (PCa) is one of the most common carcinomas in men, and aberrant expression of SEPTIN5 (SEPT5) has been detected in PCa tissues. However, the role of SEPT5 in PCa is still unclear. In this study, we attempted to explore the expression changes, clinical relevance and immunomodulatory function of SEPT5 in PCa. Methods: The expression and clinical significance of SEPT5 were evaluated based on bioinformatic analysis and were verified by western blotting, real time PCR and IHC. Allograft mouse models were used to assess the role of SEPT5 on PCa tumour formation and immunomodulatory function. Mass cytometry and IHC were used to determine the effects of SEPT5 on immune cell infiltration, especially CD8+ T cell infiltration. Correlations between SEPT5 expression and cytokine gene expression were analyzed based on TCGA and DKFZ datasets. RNA-seq and chemokine array were performed to confirm the effects of SEPT5 on cytokine production. Results: High SEPT5 expression was found in PCa and was associated with PCa prognosis. Importantly, downregulation of SEPT5 inhibited PCa progression in vivo. In addition, SEPT5 expression was negatively correlated with immune infiltrating cell levels, chemokine and cytokine gene expression associated with CD8+ T cell infiltration and activation. Downregulation of SEPT5 increased the proportion of immune cells, especially CD8+ T cells, in tumour tissue. Both the expression of CCL5, CXCL5, CXCL9, CXCL10 and INFGR1 were elevated in mRNA and protein levels after SEPT5 knockdown. Conclusions: In summary, downregulation of SEPT5 inhibited PCa progression, which may be mediated by increasing immune cell infiltration levels, especially CD8+ T cells, by promoting the production of IFNG-inducible chemokines and cytokines expression associated with immune cell infiltration. Our findings suggest that SEPT5 may serve as a prognostic biomarker of PCa and may be a target molecule to enhance the efficacy of immunotherapy for PCa in the future.

Dataset Information

Norepinephrine inhibits CD8⁺ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.

Background

Methods

Results

Conclusion

Publications

Norepinephrine inhibits CD8<sup>+</sup> T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Norepinephrine inhibits CD8+ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.

Background

Methods

Results

Conclusion

Publications

Norepinephrine inhibits CD8<sup>+</sup> T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Norepinephrine inhibits CD8⁺ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma.