Analysis of the role of the interleukins in colon cancer

Wei, Xiao‐Hong; Zhang, Yuan; Zhou, Yang; Sha, Yeqin; Pan, Yuning; Chen, Yu‐Sheng; Cai, Lei

doi:10.1186/s40659-020-00287-2

Cited by 16 publications

(17 citation statements)

References 27 publications

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“…The coding product of IL7 gene is interleukin-7, and the combination of IL7 and its receptor IL7R is essential for T cells (45). It has been reported that IL7 can inhibit the development of colon cancer, and the level of IL7 in colon cancer samples is signi cantly reduced (10), which is consistent with our results. IL7 may play an anti-tumor role through apoptosis pathway [48]In addition, IL7 can also enhance the anti-tumor immunity by combining other factors to enhance the function of immune cells (46).…”

Section: Discussionsupporting

confidence: 91%

“…aging-related genes(ARGs) play an important role in cell senescence and apoptosis. The expression of sense-cence genes can inhibit tumor cell proliferation and activate the body's speci c immune response by promoting tumor cell senescence and apoptosis, and promote the killing and elimination of tumor cells (5,10,11). However, the high expression of some ARGs can also inhibit tumor cell senescence and apoptosis (12,13).…”

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confidence: 99%

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Effect of Aging-Related Genes on the Prognosis of Colon Cancer

Liu

Gong

Huang

et al. 2021

Preprint

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Background:Colon cancer is a common malignant cancer with high incidence and poor prognosis. Cell senescence and apoptosis are important mechanisms of tumor occurrence and development, in which aging-related genes(ARGs) play an important role. This study aimed to establish a prognostic risk model based on ARGs for diagnosis and prognosis prediction of colon cancer .Methods: We downloaded transcriptome data and clinical information of colon cancer patients from the Cancer Genome Atlas(TCGA) database and the microarray dataset(GSE39582) from the Gene Expression Omnibus(GEO) database. Univariate COX, least absolute shrinkage and selection operator(LASSO) regression algorithm and multivariate COX regression analysis were used to construct a 6-ARG prognosis model and calculated the riskScore. The prognostic signatures is validated by internal validation cohort and external validation cohort(GSE39582).In addition, functional enrichment pathways and immune microenvironment of aging-related genes(ARGs) were also analyzed. We also analyzed the correlation between rsikScore and clinical features and constructed a nomogram based on riskScore. We are the first to construct prognostic nomogram based on ARGs.Results: Through univariate COX,LASSO regression algorithm and multivariate COX regression analysis,6 prognostic ARGs (PDPK1,RAD52,GSR,IL7,BDNF and SERPINE1) were screened out and riskScore was constructed. We have verified that riskScore has good prognostic value in both internal validation cohort and external validation cohort. Pathway enrichment and immunoanalysis of ARGs provide a direction for the treatment of colon cancer patients. We also found that riskScore was closely related to the clinical characteristics of patients. Based on riskScore and related clinical features, we constructed a nomogram, which has good predictive performance.Conclusion: The 6-ARG prognostic signature we constructed has a certain clinical predictive ability. Its riskScore is also closely related to clinical characteristics, and nomogram based on this has stronger predictive ability than a single indicator. ARGs and the nomogram we constructed may provide a promising treatment for colon cancer patients.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Effect of Aging-Related Genes on the Prognosis of Colon Cancer

Liu

Gong

Huang

et al. 2021

Preprint

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“…Mostly, these molecules are released during a certain time upon signal stimulation and the period of their action is most likely a reduced one, because of their limited life span in circulation [ 80 ]. Being part of the cytokine family, IL-1 family has been identified as a class of molecules, which mediate cellular communication within the immune system, possess multiple immunomodulatory functions, and participate in the regulation of tumor microenvironment [ 81 ]. Among them, IL-1 β and IL-18 are proinflammatory cytokines [ 82 ] and their actions during carcinogenesis development and progression will be further discussed.…”

Section: Molecular Inflammatory Events During Cancer Development Amentioning

confidence: 99%

Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis

Balahura

Șelaru

Dinescu

et al. 2020

Journal of Immunology Research

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Over the past decade, it has been well established that tumorigenesis is affected by chronic inflammation. During this event, proinflammatory cytokines are produced by numerous types of cells, such as fibroblasts, endothelial cells, macrophages, and tumor cells, and are able to promote the initiation, progression, and metastasis of different types of cancer. When persistent inflammation occurs, activation of inflammasome complexes is initiated, leading to its assembly and further activation of caspase, production of proinflammatory cytokines, and pyroptosis induction. The function of this multiprotein complex is not only to reassure inflammation and to promote cell death, through caspase activity, but also has been identified to have significant contributions during tumorigenesis and cancer development. So far, many efforts have been made in order to extend the knowledge of inflammasome implications and how its components could be targeted as therapeutic agents. Additionally, microRNAs (miRNAs), evolutionary conserved noncoding molecules, have emerged as pivotal players during numerous biological events by regulating gene and protein expression. Therefore, dysregulations of miRNA expressions have been correlated with inflammation during tumor development. In this review, we aim to highlight the dual role of inflammasomes and proinflammatory cytokines during carcinogenesis paired with the distinguished effects of miRNAs upon inflammation cascades during tumor growth and progression.

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“…Human interleukin-7 (IL-7) is a pleiotrophic cytokine with a wide range of immune effects, which exhibits a direct or indirect role in the anti-tumor effect; it can also affect the growth, survival, and differentiation of B and T cells ( 5 ). At present, IL-7 application in immunotherapy has entered the clinical trial phase and achieved certain curative effects, including the cases of melanoma, lymphoma, and colon cancer ( 6 – 8 ). To date, clinical data have consistently demonstrated that IL-7 co-expression can prolong the survival time of CAR-T cells and improve their ability to expand and kill tumors ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

IL-7 and CCR2b Co-Expression-Mediated Enhanced CAR-T Survival and Infiltration in Solid Tumors

Zhang

Han

et al. 2021

Front. Oncol.

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Chimeric antigen receptor T (CAR-T) cells are not effective in solid tumor treatment due to reduced invasion and expansion, and short survival time. This study aimed to explore whether interleukin (IL)-7 and CCR2b expression could improve GD2-CAR-T cell survival and infiltration in neuroblastoma and melanoma treatment. IL-7 and CCR2b were inserted into the classical second-generation CAR structure to construct 7×2b CAR. The 7×2b CAR-T cell phenotypes were evaluated by flow cytometry and the chemokine levels by ELISA. The 7×2b CAR-T cell migration and anti-tumor abilities were detected by Transwell assay and animal experiments in vivo. We report that compared with that of CAR-T cells, 7×2b CAR-T cell IL-7 secretion and CCR2b expression did not affect the T cell surface expression of CAR or CAR-T specificity and efficacy against tumor cells. The 7×2b CAR-T cells could induce IFN-γ secretion in GD2-positive tumor cells, killing them as well as conventional CAR-T cells. Moreover, IL-7 and CCR2b co-expression enhanced the 7×2b CAR-T cell survival and migration. Similar to conventional CAR-T, 7×2b CAR-T cells could also inhibit tumor growth and increase IFN-γ, Gzms-B, and IL-2 expression. Finally, unlike in mice injected with CAR-T cells, CD3 expression was the most abundant in the spleen and tumor tissues in mice injected with 7×2b CAR-T cells. Our study demonstrates that IL-7 and CCR2b co-expression in GD2-CAR-T cells exhibit stronger anti-tumor activity than classical second-generation CAR-T cells, shedding light on the potential novel GD2-positive neuroblastoma and melanoma treatment approach.

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Analysis of the role of the interleukins in colon cancer

Cited by 16 publications

References 27 publications

Effect of Aging-Related Genes on the Prognosis of Colon Cancer

Effect of Aging-Related Genes on the Prognosis of Colon Cancer

Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis

IL-7 and CCR2b Co-Expression-Mediated Enhanced CAR-T Survival and Infiltration in Solid Tumors

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