Immunometabolism: a new dimension in immunotherapy resistance

Xiao, Chaoyue; Xiong, Wei; Xu, Yiting; Zou, Ji’an; Zeng, Yue; Liu, Junqi; Peng, Yurong; Hu, Chunhong; Wu, Fang

doi:10.1007/s11684-023-1012-z

Cited by 5 publications

(1 citation statement)

References 280 publications

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“…However, the use of immune checkpoint inhibitors alone leaves some patients unresponsive to therapy, and patients may develop resistance to therapy over time [13,14]. Additionally, immune-related adverse reactions, such as autoimmune reactions, may occur, limiting the use of these inhibitors [15,16].…”

mentioning

confidence: 99%

Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine of IFNα and is enhanced by CD47 blockade

Li,

Luo,

et al. 2023

Preprint

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Background Immunotherapy has greatly changed the landscape of cancer therapy; however, only a subset of patients responds to immune checkpoint blockade or to CAR-T based therapy. Previously, we demonstrated that natural host-defence peptide caerin1.1/caerin1.9 (F1/F3) increases the efficacy of anti-PD-1 and therapeutic vaccine, in a HPV16 + TC-1 tumour model, but the anti-tumor mechanism of F1/F3 is still unclear. Methods In this study, we explored the impact of F1/F3 on the tumor microenvironment in a transplanted B16 melanoma model, and further investigated the mechanism of action of F1/F3 using monoclonal antibodies to deplete relevant cells, gene knockout mice and flow cytometry. Results we show that F1/F3 is able to inhibit the growth of melanoma B16 tumour cells both in vitro and in vivo. Depletion of macrophages, blockade of IFNα receptor, and Stat1 inhibition each abolishes F1/F3-mediated antitumor responses. Subsequent analysis reveals that F1/F3 increases the tumour infiltration of inflammatory macrophages, upregulates the expression of IFNα receptor, and promotes the secretion of IFNα by macrophages. Interestingly, F1/F3 upregulates CD47 expression on tumour cells; and blocking CD47 increases F1/F3-mediated antitumor responses. Furthermore, F1/F3 intratumor injection, CD47 blockade, and therapeutic vaccination significantly increases the survival time of B16 tumour-bearing mice. These results indicate that F1/F3 may be effective to improve the efficacy of ICB and therapeutic vaccine-based immunotherapy for human epithelial cancers and warrants consideration for clinical trials.

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confidence: 99%

Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine of IFNα and is enhanced by CD47 blockade

Li,

Luo,

et al. 2023

Preprint

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Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer

Wang,

Guo,

Sun

et al. 2024

Phytomedicine

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Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

Hu,

Liu,

Lei

et al. 2024

Sig Transduct Target Ther

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Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes and functions of immune cells. The metabolic regulation of the immune system is important in the pathogenesis and progression of numerous diseases, such as cancers, autoimmune diseases and metabolic diseases. The concept of immunometabolism was introduced over a decade ago to elucidate the intricate interplay between metabolism and immunity. The definition of immunometabolism has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. With immunometabolism being proposed and developed, the metabolic regulation of the immune system can be gradually summarized and becomes more and more clearer. In the context of many diseases including cancer, autoimmune diseases, metabolic diseases, and many other disease, metabolic reprogramming occurs in immune cells inducing proinflammatory or anti-inflammatory effects. The phenotypic and functional changes of immune cells caused by metabolic regulation further affect and development of diseases. Based on experimental results, targeting cellular metabolism of immune cells becomes a promising therapy. In this review, we focus on immune cells to introduce their metabolic pathways and metabolic reprogramming, and summarize how these metabolic pathways affect immune effects in the context of diseases. We thoroughly explore targets and treatments based on immunometabolism in existing studies. The challenges of translating experimental results into clinical applications in the field of immunometabolism are also summarized. We believe that a better understanding of immune regulation in health and diseases will improve the management of most diseases.

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Immunometabolism: a new dimension in immunotherapy resistance

Cited by 5 publications

References 280 publications

Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine of IFNα and is enhanced by CD47 blockade

Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine of IFNα and is enhanced by CD47 blockade

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer

Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

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