The Intestinal Tumour Microenvironment

Leman, Julia Koehler; Munoz‐Erazo, Luis; Kemp, Roslyn A.

doi:10.1007/978-3-030-36214-0_1

Cited by 13 publications

(12 citation statements)

References 121 publications

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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

105

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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

105

View full text Add to dashboard Cite

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“…In recent years, many studies have shown that the tumor microenvironment significantly affects tumor growth and progression and offers potential value in the diagnosis and prognosis prediction of tumors 5 – 10 . Moreover, it has been reported that the tumor microenvironment highly influences the progression of colorectal cancer 5 , 11 . Recently, with the rapid development of precision medicine, more and more researchers are using statistical algorithms to explore new diagnostic and therapeutic targets of cancer.…”

Section: Introductionmentioning

confidence: 99%

Identification of tumor microenvironment-related prognostic genes in colorectal cancer based on bioinformatic methods

Liu

Cheng

et al. 2021

Sci Rep

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Colorectal cancer (CRC) ranks fourth among the deadliest cancers globally, and the progression is highly affected by the tumor microenvironment (TME). This study explores the relationship between TME and colorectal cancer prognosis and identifies prognostic genes related to the CRC microenvironment. We collected the gene expression data from The Cancer Genome Atlas (TCGA) and calculated the scores of stromal/immune cells and their relations to clinical outcomes in colorectal cancer by the ESTIMATE algorithm. Lower immune scores were significantly related to the malignant progression of CRC (metastasis, p = 0.001). We screened 292 differentially expressed genes (DEGs) by dividing CRC cases into high and low stromal/immune score groups. Functional enrichment analyses and protein–protein interaction (PPI) networks illustrated that these DEGs were closely involved in immune response, cytokine–cytokine receptor interaction, and chemokine signaling pathway. Six DEGs (FABP4, MEOX2, MMP12, ERMN, TNFAIP6, and CHST11) with prognostic value were identified by survival analysis and validated in two independent cohorts (GSE17538 and GSE161158). The six DEGs were significantly related to immune cell infiltration levels based on the Tumor Immune Estimation Resource (TIMER). The results might contribute to discovering new diagnostic and prognostic biomarkers and new treatment targets for colorectal cancer.

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“…The TME is multicellular and consists of a highly complex interaction between the tumor cells, stromal cells, immune cells, and microorganisms ( 9 ). This multicellular interaction, based on soluble factors, transformed ECM, epigenetic modifications, immune cells, and transformed fibroblasts, not only induces the malignancy and metastasis of tumors but also delays and blocks the response to tumor treatment leading to the acquisition of drug resistance ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment

et al. 2021

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BackgroundTumor microenvironment (TME) provides the essential prerequisite niche for promoting cancer progression and metastasis. Calebin A, a component of Curcuma longa, has long been investigated as a safe multitargeted agent with antitumor and anti-inflammatory properties. However, the multicellular-TME-induced malignancy and the antitumorigenic potential of Calebin A on colorectal cancer (CRC) cells in 3D-alginate cultures are not yet understood, and more in-depth research is needed.Methods3D-alginate tumor cultures (HCT116 cells) in the multicellular proinflammatory TME (fibroblast cells/T lymphocytes), tumor necrosis factor beta (TNF-β)-TME (fibroblast cells/TNF-β) were treated with/without Calebin A to address the pleiotropic actions of Calebin A in the CRC.ResultsWe found that Calebin A downmodulated proliferation, vitality, and migration of HCT116 cells in 3D-alginate cultures in multicellular proinflammatory TME or TNF-β-TME. In addition, Calebin A suppressed TNF-β-, similar to multicellular-TME-induced phosphorylation of nuclear factor kappa B (NF-κB) in a concentration-dependent manner. NF-κB-promoting proinflammatory mediators, associated with tumor growth and antiapoptotic molecules (i.e.,MMP-9, CXCR4, Ki-67, β1-integrin, and Caspase-3) and its translocation to the nucleus in HCT116 cells, were increased in both TME cultures. The multicellular-TME cultures further induced the survival of cancer stem cells (CSCs) (upregulation of CD133, CD44, and ALDH1). Last but not the least, Calebin A suppressed multicellular-, similar to TNF-β-TME-induced rigorous upregulation of NF-κB phosphorylation, various NF-κB-regulated gene products, CSCs activation, and survival in 3D-alginate tumor cultures.ConclusionsThe downmodulation of multicellular proinflammatory-, similar to TNF-β-TME-induced CRC proliferation, survival, and migration by the multitargeting agent Calebin A could be a new therapeutic strategy to suppress inflammation and CRC tumorigenesis.

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The Intestinal Tumour Microenvironment

Cited by 13 publications

References 121 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

Identification of tumor microenvironment-related prognostic genes in colorectal cancer based on bioinformatic methods

Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment

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