Correlations Between Serum IL33 and Tumor Development: a Meta-analysis

Chen, Xiangjun; Huang, Ying-De; Li, Nian; Chen, Min; Liu, Fang; Pu, Dan; Zhou, Tao-You

doi:10.7314/apjcp.2014.15.8.3503

Cited by 14 publications

(11 citation statements)

References 23 publications

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“…Recently, it has been reported that IL‐33 is overexpressed in carcinoma tissue and elevated in serum of HCC patients . Additionally, soluble ST2, a factor that binds and inactivates IL‐33, was detected to be a negative prognostic factor in HCC .…”

Section: Discussionmentioning

confidence: 99%

“…A member of the IL‐1 family, IL‐33 acts as a driver of type 2 inflammatory conditions such as asthma, fibrosis, rheumatic disease, and response to parasites and is able to prolong allograft survival . In the setting of cancer, IL‐33 is detected at elevated levels and seems to have pleiotropic functions . In breast cancer IL‐33 promotes cancer progression and metastasis by intratumoral accumulation of immunosuppressive cells and by diminishing innate antitumor immunity .…”

mentioning

confidence: 99%

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Tumor‐infiltrating, interleukin‐33–producing effector‐memory CD8+ T cells in resected hepatocellular carcinoma prolong patient survival

Brunner¹,

Rubner²,

Kesselring³

et al. 2015

Hepatology

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Interleukin‐33 (IL‐33), a cytokine with pleiotropic functions, is elevated in serum of patients with hepatocellular carcinoma (HCC). This study investigated the effects of local IL‐33 expression in resected HCC on patient survival and on the immunological and molecular tumor microenvironment. Tissue of resected HCCs was stained for hematoxylin and eosin, Masson trichrome, alpha‐smooth muscle actin, IL‐33, CD8, and IL‐13 and analyzed by flow cytometry. Besides histomorphologic evaluation, the immunohistochemical stainings were analyzed for the respective cell numbers separately for tumor area, infiltrative margin, and distant liver stroma. These findings were correlated with clinical data and patient outcome. Further, gene expression of different HCC risk groups was compared using microarrays. In multivariable analysis, infiltration of HCCs by IL‐33+ cells (P = 0.032) and CD8+ cells (P = 0.014) independently was associated with prolonged patient survival. Flow cytometry demonstrated that cytotoxically active subpopulations of CD8+ cells, in particular CD8+CD62L–KLRG1+CD107a+ effector‐memory cells, are the main producers of IL‐33 in these HCC patients. Using infiltration by IL‐33+ and CD8+ cells as two separate factors, an HCC immune score was designed and evaluated that stratified patient survival (P = 0.0004). This HCC immune score identified high‐ and low‐risk patients who differ in gene expression profiles (P < 0.001). Conclusion: Infiltration of HCCs by IL‐33+ and CD8+ cells is independently associated with prolonged patient survival. We suggest that this is due to an induction of highly effective, cytotoxically active CD8+CD62L–KLRG1+CD107a+ effector‐memory cells producing IL‐33. Based on these two independent factors, we established an HCC immune score that provides risk stratification for HCC patients and can be used in the clinical setting. (Hepatology 2015;61:1957‐1967)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Tumor‐infiltrating, interleukin‐33–producing effector‐memory CD8+ T cells in resected hepatocellular carcinoma prolong patient survival

Brunner¹,

Rubner²,

Kesselring³

et al. 2015

Hepatology

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“…High ST2 and IL-33 mRNA levels have been identified in colonic adenomas and carcinomas compared to normal tissue [9], and higher expression has been described in poorly differentiated human colorectal carcinoma cells [80]. In addition, high IL-33 serum levels have been identified in patients with lung, gastric and hepatocellular carcinoma [81,82], and high sST2 serum levels have been detected in patients with breast cancer and hepatocellular carcinoma [83,84]. There may be an association between IL-33 serum levels and progression or stage of a number of cancers [82], suggesting that IL-33 and ST2 may be used as prognostic marker of disease.…”

Section: Cancermentioning

confidence: 99%

The IL-33/ST2 axis: Role in health and disease

Fuente

MacDonald

Hermoso

2015

Cytokine & Growth Factor Reviews

148

107

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“…Given the importance of inflammation in cancer, recent studies have begun to investigate the role of IL-33 and its receptor ST2 (also termed IL1R1) in CRC [70]. Indeed, IL-33 is elevated in the serum of patients with lung, gastric and hepatocellular cancer [71] and is a marker for poor prognosis [11, 69]. Previous work showed that higher expression of total IL-33 and ST2 correlates with CRC progression and metastasis, with inhibition of IL-33 in CRC cells resulting in reduced cell migration, colony formation and tumor growth in vitro, and smaller tumors in vivo [72, 73].…”

Section: Introductionmentioning

confidence: 99%

A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer

et al. 2017

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Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences contain multiple regulatory motifs and hence are capable of influencing expression of host genes. TEs are known to be released from epigenetic repression and can become transcriptionally active in cancer. Such activation could also lead to lineage-inappropriate activation of oncogenes, as previously described in lymphomas. However, there are few reports of this mechanism occurring in non-blood cancers. Here, we re-analyzed whole transcriptome data from a large cohort of patients with colon cancer, compared to matched normal colon control samples, to detect genes or transcripts ectopically expressed through activation of TE promoters. Among many such transcripts, we identified six where the affected gene has described role in cancer and where the TE-driven gene mRNA is expressed in primary colon cancer, but not normal matched tissue, and confirmed expression in colon cancer-derived cell lines. We further characterized a TE-gene chimeric transcript involving the Interleukin 33 (IL-33) gene (termed LTR-IL-33), that is ectopically expressed in a subset of colon cancer samples through the use of an endogenous retroviral long terminal repeat (LTR) promoter of the MSTD family. The LTR-IL-33 chimeric transcript encodes a novel shorter isoform of the protein, which is missing the initial N-terminus (including many conserved residues) of Native IL-33. In vitro studies showed that LTR-IL-33 expression is required for optimal CRC cell line growth as 3D colonospheres. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in colon cancer.

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Correlations Between Serum IL33 and Tumor Development: a Meta-analysis

Cited by 14 publications

References 23 publications

Tumor‐infiltrating, interleukin‐33–producing effector‐memory CD8+ T cells in resected hepatocellular carcinoma prolong patient survival

Tumor‐infiltrating, interleukin‐33–producing effector‐memory CD8+ T cells in resected hepatocellular carcinoma prolong patient survival

The IL-33/ST2 axis: Role in health and disease

A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer

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