Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Li, Saiyang; Huang, Chih Chia; Hu, Guanghui; Ma, Junjie; Chen, Yonghui; Zhang, Jin; Huang, Yiran; Zheng, Junhua; Xue, Wei; Xu, Yunfei; Zhai, Wei

doi:10.1038/s41419-020-2355-x

Cited by 26 publications

(25 citation statements)

References 47 publications

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“…B-cells are more easily recruited in renal carcinoma tissues than in normal renal tissues. The interaction between B-cells and cancer cells allows IL-1β secretion, which is responsible for renal cancer cell migration, through HIF-2α and Notch1 pathways [ 216 ]. Production of IL-1β by cancer cells or neighboring cells can activate many molecular pathways that lead to cancer cell migration.…”

Section: Pro-and Anti-tumor Effects Of Il-1βmentioning

confidence: 99%

Interleukin-1β and Cancer

Rébé

Ghiringhelli

2020

Cancers

198

110

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Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment.

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Section: Pro-and Anti-tumor Effects Of Il-1βmentioning

confidence: 99%

Interleukin-1β and Cancer

Rébé

Ghiringhelli

2020

Cancers

198

110

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“…1 b) [ 19 , 69 ]. Recent studies have shown that up-regulated expression of interleukin-1β (IL-1β) secreted by B cells promotes the activation of HIF-2α, and HIF-2α activation further promotes the activation of delta like canonical Notch ligand 4 (DLL4) signaling, and finally interact with neurogenic locus notch homolog (Notch) to form the IL-1β/HIF-2α/Notch 1 axis [ 70 ]. Collectively, various mechanisms drive HIF signaling activation in low oxygen tensions to maintain the state of various cancer cell types, and TNF-α interacts with HIF signaling provides a preferable and typical example.…”

Section: Canonical and Non-canonical Regulation Of Hif Signalingmentioning

confidence: 99%

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Mao

Wang

et al. 2020

J Exp Clin Cancer Res

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Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors.

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“…[ 4 , 5 ]. Tumor cells and the components of TME, including CD8 + T cells [ 6 , 7 ], CD4 + T cells [ 8 , 9 ], NK cells [ 10 ], dendritic cells [ 11 , 12 ], B cells [ 13 , 14 ], macrophages [ 15 ], FOXP3 [ 16 ], and Collagen I [ 17 ] have close correlations to tumor treatment and prognosis. In past decades, due to the limitations of tools and clinical methodologies, it was difficult to analyze multiple components and assess tumor heterogeneity of the TME.…”

Section: Introductionmentioning

confidence: 99%

Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis

Xie

Zhang

Shan

et al. 2021

Journal of Immunology Research

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Background. Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. Methods. We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. Results. Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. Conclusion. The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.

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Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Cited by 26 publications

References 47 publications

Interleukin-1β and Cancer

Interleukin-1β and Cancer

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis

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