Inflammation and Cancer: Triggers, Mechanisms, and Consequences

Greten, Florian R.; Grivennikov, Sergei I.

doi:10.1016/j.immuni.2019.06.025

Cited by 2,556 publications

(1,972 citation statements)

References 184 publications

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“…In the early stage of tumorigenesis, inflammatory cells can become influential tumor promoters, creating a favorable environment for tumor growth and promoting blood vessel growth [17][18][19]. Many factors have been found to be related to the occurrence of MVI in HCC; in this study, it is suggested that GLR is positively correlated with AST, and NEUT, AST, GLR and other inflammatory factors' level in the MVI group are higher than those in the non-MVI group, suggesting that these inflammatory factors may promote HCC progression and increase risk of MVI, which is in accordance with the researches which illuminate that anti-inflammatory treatment can effectively prevent early tumorigenesis and later malignant transformation [20,21] .…”

Section: Discussionsupporting

confidence: 88%

Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion

Zhang

Zhou

et al. 2020

BMC Cancer

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Background: Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment. Methods: From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients. Results:The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p < 0.001), respectively. According to ROC curve analysis, the optimal cut-off value of GLR was 56.0, and the area under the ROC curve (AUC) was 0.781 (95% CI, 0.719-0.833) for the risk prediction of MVI in HCC patients. Multivariate analysis showed that tumor size > 5 cm, HCC combined with MVI and GLR > 56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS).Conclusion: GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI.

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Section: Discussionsupporting

confidence: 88%

Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion

Zhang

Zhou

et al. 2020

BMC Cancer

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“…Tumor-associated immune cells and their crosstalk with cancer and the components of its microenvironment dramatically affect tumor behavior and patient outcome [1,2]. The concept of cancer immunoediting, represents the dynamic of this interaction, which runs through the phases of elimination, equilibrium and escape, and explains how immunosuppression can overwhelm immunosurveillance [3], eliciting the development of immunological-based approaches to cancer treatment [4,5].…”

Section: Introductionmentioning

confidence: 99%

Decoding the Role of Interleukin-30 in the Crosstalk between Cancer and Myeloid Cells

Carlo

2020

Cells

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In the last few years, a new actor hit the scene of the tumor microenvironment, the p28 subunit of interleukin (IL)-27, known as IL-30. Its molecular structure allows it to function as an autonomous cytokine and, alternatively, to pair with other subunits to form heterodimeric complexes and enables it to play different, and not fully elucidated, roles in immunity. However, data from the experimental models and clinical samples, suggest IL-30 s engagement in the relationship between cancer and myeloid cells, which fosters the tumor microenvironment and the cancer stem cell niche, boosting the disease progression. Activated myeloid cells are the primary cellular source and one of the targets of IL-30, which can also be produced by cancer cells, especially, in aggressive tumors, as observed in the breast and prostate. This review briefly reports on the immunobiology of IL-30 and related cytokines, by comparing mouse and human counterparts, and then focuses on the mechanisms whereby IL-30 amplifies intratumoral myeloid cell infiltrate and triggers a vicious cycle that worsens immunosuppression in the tumor microenvironment (TME) and constitutes a real threat for a successful immunotherapeutic strategy.Cells 2020, 9, 615 2 of 14 of reactive oxygen species (ROS), nitric oxide (NO), and ectoenzymes, which regulate the adenosine metabolism; expression of immune checkpoint molecules [10,11]; depletion of metabolites critical for lymphocyte functions [12,13]; and through their secretion of growth, angio-lymph-angiogenic factors and inflammatory mediators [13], that are crucial for tissue remodeling and tumor development.Recent insights into this inflammatory milieu, specifically in breast (BC) and prostate (PC) cancers, have unveiled a role for the novel immunoregulatory mediator Interleukin(IL)-30/IL-27p28 [14] in the TME and in the intricate relationship between cancer and myeloid cells, which orchestrates tumor-promoting events with evident clinical implications [15,16].

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“…Colon cancer, like some other solid malignancies, is infiltrated by various types of immune cells such as tumor-associated macrophages (TAMs), monocytes, neutrophils, and mast cells, which contribute to an inflammatory microenvironment (Greten & Grivennikov, 2019;Komohara, Fujiwara, Ohnishi, & Takeya, 2016). Inflammatory microenvironment can regulate cancer progression and affect many facets of cancer development, including cell proliferation, angiogenesis, invasion, and metastasis (Greten & Grivennikov, 2019). TAMs are a well-known component of inflammatory infiltrates and key producer of inflammatory cytokines and chemokines (Pathria, Louis, & Varner, 2019).…”

Section: Introductionmentioning

confidence: 99%

c‐Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment

Ding

Hao

et al. 2019

Journal Cellular Physiology

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Inflammatory microenvironment is an important factor for promoting cancer invasion and metastasis, but the underlying molecular mechanisms remain unclear. Here, we mimicked an inflammatory microenvironment both in vitro and in vivo and investigated its effects on the invasion and metastasis of colon cancer. Moreover, colon cancer patient samples were also analyzed statistically. Conditioned medium from the differentiated macrophages induced invasion and migration of colon cancer cells in vitro, which could be reversed by the treatment of a neutralizing anti-growth differentiation factor 15 (GDF15) antibody, indicating GDF15 involvement in inflammation-induced invasiveness. Also, we observed similar effects of human recombinant GDF15 on colon cancer cells. Mechanistically, GDF15 activated c-Fos by separating it from Lamin A/C, increasing transcriptional activity of c-Fos and regulating EMT gene expressions. However, c-Fos knockdown using lentivirus shRNA plasmid inhibited GDF15-triggered invasion and migration in vitro. In vivo, inflammation caused by lipopolysaccharides obviously increased GDF15 secretion, and c-Fos knockdown reduced the lung metastasis of colon cancer cells in mice model. In addition, c-Fos expressions in patient samples were found to be associated with colon cancer metastasis and TNM stages. Taken together, GDF15 in inflammatory microenvironment induces colon cancer invasion and metastasis by regulating EMT genes by activating c-Fos, which might be a potential therapeutic target for metastatic colon cancer. K E Y W O R D S EMT, Erk1/2, Lamin A/C/c-Fos signaling axis, macrophages-derived cytokine Abbreviations: CM, conditioned medium; DAPI, diamidinophenylindole; EMSA, electrophoretic mobility shift assays; EMT, epithelial-mesenchymal transition; GDF15, growth differentiation factor 15; H&E, hematoxylin and eosin; IH C, immunohistochemistry; LPS, lipopolysaccharides; PMA, phorbol 12-myristate 13-acetate; RM, regular medium; TAMs, tumor-associated macrophages. *Youxiang Ding and Kun Hao contributed equally to this work. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Ding Y, Hao K, Li Z, et al. c-Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment.

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Inflammation and Cancer: Triggers, Mechanisms, and Consequences

Cited by 2,556 publications

References 184 publications

Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion

Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion

Decoding the Role of Interleukin-30 in the Crosstalk between Cancer and Myeloid Cells

c‐Fos separation from Lamin A/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment

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