The Role of Interleukins in Colorectal Cancer

Li, Jingjing; Huang, Ling; Zhao, Han; Yan, Yichao; Lü, Jing

doi:10.7150/ijbs.46651

Cited by 96 publications

(105 citation statements)

References 144 publications

(183 reference statements)

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“…Colorectal cancer (CRC) is, like any other cancer, a complex disease with a high prevalence globally. Malignant epithelial cancer cells are supported by the tumor microenvironment, which includes various immune cells, cancer-associated fibroblasts, and circulating cytokines [ 120 , 121 ], many of which have been demonstrated to promote CRC progression [ 122 ]. Cytokines promoting tumorigenesis are IL-4, IL-6, IL-8, IL-11, IL-17A, IL-22, IL-23, IL-33, TNF-α, TGF-β, and VEGF (vascular endothelial growth factor), whereas cytokines with antitumorigenic properties are IFN-γ, IL-12, IL-15, IL-17F, and IL-18.…”

Section: Cytokine Regulation In Intestinal Pathologymentioning

confidence: 99%

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

Mahapatro

Erkert

Becker

2021

Cells

104

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Cytokines are small proteins that are secreted by a vast majority of cell types in the gut. They not only establish cell-to-cell interactions and facilitate cellular signaling, but also regulate both innate and adaptive immune responses, thereby playing a central role in genetic, inflammatory, and infectious diseases of the gut. Both, immune cells and gut epithelial cells, play important roles in intestinal disease development. The epithelium is located in between the mucosal immune system and the gut microbiome. It not only establishes an efficient barrier against gut microbes, but it also signals information from the gut lumen and its composition to the immune cell compartment. Communication across the epithelial cell layer also occurs in the other direction. Intestinal epithelial cells respond to immune cell cytokines and their response influences and shapes the microbial community within the gut lumen. Thus, the epithelium should be seen as a translator or a moderator between the microbiota and the mucosal immune system. Proper communication across the epithelium seems to be a key to gut homeostasis. Indeed, current genome-wide association studies for intestinal disorders have identified several disease susceptibility loci, which map cytokine signatures and their related signaling genes. A thorough understanding of this tightly regulated cytokine signaling network is crucial. The main objective of this review was to shed light on how cytokines can orchestrate epithelial functions such as proliferation, cell death, permeability, microbe interaction, and barrier maintenance, thereby safeguarding host health. In addition, cytokine-mediated therapy for inflammation and cancer are discussed.

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Section: Cytokine Regulation In Intestinal Pathologymentioning

confidence: 99%

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

Mahapatro

Erkert

Becker

2021

Cells

104

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“…IL-6 forms a complex with the IL-6 receptor, leading to persistent activation of STAT3 53 . The levels of IL-6 are dramatically increased in serum and tumor samples of humans and mice with colorectal cancer, and high IL-6 levels in colorectal cancers are found to correlate with poor prognosis 54 - 55 . IL-6 promotes the survival of colon carcinoma cells in vitro ; however blocking IL-6 signal prevents tumor growth 56 - 57 .…”

Section: Discussionmentioning

confidence: 99%

MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway

Zhao¹,

Cheng²,

Guo³

et al. 2021

Int. J. Biol. Sci.

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Mixed lineage kinase domain-like protein (MLKL) plays an important role in necroptosis, but the role and mechanism of MLKL in intestinal tumorigenesis remain unclear. Here, we found that hematopoietic- and nonhematopoietic-derived MLKL affected intestinal inflammation, but nonhematopoietic-derived MLKL primarily inhibited intestinal tumorigenesis. Loss of MLKL enhanced intestinal regeneration and the susceptibility to intestinal tumorigenesis in Apc min/+ mice by hyperactivating the Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, MLKL deficiency increased interleukin-6 (IL-6) production in dendritic cells. Administration of anti-IL-6R antibody therapy reduced intestinal tumorigenesis in Apc min/+ Mlkl -/- mice. Notably, low MLKL expression in human colorectal tumors, which enhanced STAT3 activation, was associated with decreased overall survival. Together, our results reveal that MLKL exhibits a suppressive effect during intestinal tumorigenesis by suppressing the IL-6/JAK2/STAT3 signals.

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“…Researchers have reported both the tumor-promoting and suppressive effects of the IL-1 pathway. Generally, IL-1 promotes tumorigenesis and tumor metastasis in CRC [ 51 ]. In colorectal specimens from patients with CRC, the expression of Il1b was higher in CRC tumors than in normal colorectal mucosa [ 52 ].…”

Section: Microbiota Inflammatory Mediators and Crcmentioning

confidence: 99%

“…STAT3 also facilitates cell invasion and migration by regulating matrix metallopeptidase-2 (MMP-2), MMP-9, and MMP-7 and modulating Rho and Rac. Angiogenesis can also be regulated by STAT3 via the upregulation of VEGF and hypoxia-inducible factor 1-alpha [ 51 , 86 ]. IL-10 interferes with the antitumor activity of the immune system by inhibiting antigen presentation in both antigen presenting cells and tumor cells and inducing T cell anergy [ 87 ].…”

Section: Microbiota Inflammatory Mediators and Crcmentioning

confidence: 99%

Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

Heo

Lee

2021

Cancers

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Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

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The Role of Interleukins in Colorectal Cancer

Cited by 96 publications

References 144 publications

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway

Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

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