Targeting inflammasome/IL-1 pathways for cancer immunotherapy

Guo, Beichu; Fu, Shunjun; Zhang, Jinyu; Liu, Bei; Li, Zihai

doi:10.1038/srep36107

Cited by 217 publications

(200 citation statements)

References 68 publications

(93 reference statements)

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“…As mentioned above, MDSCs and TAMs are key components of the tumor‐associated microenvironment that promotes tumor progression and metastasis 31,32. MDSCs rather than other myeloid cells, such as neutrophils and monocytes/macrophages, significantly increased in Brca1 mutant MG (Figure 7A), but not in Brca1 mutant tumor (Figure S9D, Supporting Information).…”

Section: Resultsmentioning

confidence: 83%

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BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis

Chen¹,

Lei²,

Bao³

et al. 2020

Advanced Science

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The breast cancer susceptibility gene 1 (BRCA1) is a major tumor suppressor gene and is most frequently mutated in hereditary breast cancer. BRCA1 plays a critical role in many biological processes, especially maintaining genomic stability in the nucleus, yet its role in the cytoplasm remains elusive. Here, it is revealed that BRCA1 maintains a healthy mitochondrial network through regulating mitochondrial dynamics, including fission and fusion. BRCA1 deficiency causes dysfunctional mitochondrial dynamics through increased expression of mitofusin1/2. With mitochondrial stress, BRCA1 is recruited to the mitochondrial outer membrane, where it plays an essential role in maintaining a healthy mitochondrial network. Consequently, BRCA1 deficiency impairs stress‐induced mitophagy through blocking ataxia‐telangiectasia mutated (ATM)‐AMP‐activated protein kinase (AMPK)‐Dynamin‐related protein 1 (DRP1)‐mediated mitochondrial fission and triggers NLRP3 inflammasome activation, which creates a tumor‐associated microenvironment, thereby facilitating tumor proliferation and metastasis. It is further shown that inflammasome inhibition can prevent tumor recurrence and metastasis. This study uncovers an important role of BRCA1 in regulating mitophagy and suggests a therapeutic approach for fighting this deadly disease.

show abstract

Section: Resultsmentioning

confidence: 83%

“…IL‐1β promotes tumor progression and counteracts immunosurveillance by recruiting myeloid cells, such as myeloid‐derived suppressor cells (MDSCs) and tumor‐associated macrophages (TAMs) 31,32. This suggests that BRCA1 mutation could establish a tumor‐associated microenvironment for cancer progression via inflammasome activation.…”

Section: Resultsmentioning

confidence: 99%

BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis

Chen¹,

Lei²,

Bao³

et al. 2020

Advanced Science

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show abstract

“…TAM and MDSC can be recruited to the tumor side by IL-1β [232]. In agreement, in a mouse breast cancer model inhibition of NLRP3 effectively reduced the tumor-resident population of MDCS [288] and TAM [232].…”

Section: Inhibition Of Il-1 Signaling Inhibits Tumor Growthmentioning

confidence: 88%

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

282

221

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Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

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“…The effect of inflammasome activation in different cancers has been determined in previous studies, including NLRC4 inflammasome activation in colorectal cancer (CRC), NLRP1 inflammasome activation in metastatic melanoma, and NLRP3 inflammasome activation in metastatic CRC as well as in breast cancer . It is intriguing that inflammasome activation can either play a positive or negative role in the tumourigenesis of different cancers.…”

Section: Metabolic Regulation Of Inflammasome Activation In Inflammatmentioning

confidence: 99%

Metabolic regulation of inflammasomes in inflammation

Yang

Liu

et al. 2019

Immunology

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Summary Inflammasome activation and subsequent inflammatory cytokine secretion are essential for innate immune defence against multiple stimuli and are regarded as a link to adaptive immune responses. Dysfunction of inflammasome activation has been discovered at the onset or progression of infectious diseases, autoimmune diseases and cancer, all of which are also associated with metabolic factors. Furthermore, many studies concerning the metabolic regulation of inflammasome activation have emerged in recent years, especially regarding the activity of the NLRP3 inflammasome under metabolic reprogramming. In this review, we discuss the molecular mechanisms of the interactions between metabolic pathways and inflammasome activation, which exerts further important effects on various diseases.

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Targeting inflammasome/IL-1 pathways for cancer immunotherapy

Cited by 217 publications

References 68 publications

BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis

BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Metabolic regulation of inflammasomes in inflammation

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