Protumor vs Antitumor Functions of IL-17

Murugaiyan, Gopal; Saha, Bhaskar

doi:10.4049/jimmunol.0901017

Cited by 322 publications

(293 citation statements)

References 111 publications

Supporting

Mentioning

278

Contrasting

Unclassified

Order By: Relevance

“…Despite the positive correlation of Th17 cells with reduced survival in HCC cases, the role of these cells in HCC still remains incompletely defined. Some studies have recently suggested that IL17 plays a dual role in tumor immunology; it can either promote antitumor cytotoxic T cell responses or foster angiogenesis of surrounding endothelial cells and fibroblasts facilitating tumor growth [52] . In HCC patients, increased levels of Th17 and Th1 cells were observed in tumor regions as compared to nontumor regions, with the frequency of these cells being associated with overall diseasefree survival [53] .…”

Section: T Lymphocytesmentioning

confidence: 99%

Immunology of hepatocellular carcinoma

Sachdeva

Chawla

Arora

2015

WJH

100

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g. , dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

show abstract

Section: T Lymphocytesmentioning

confidence: 99%

Immunology of hepatocellular carcinoma

Sachdeva

Chawla

Arora

2015

WJH

100

View full text Add to dashboard Cite

show abstract

“…These cells and the cytokines they produce (including IL-17A, IL-17F and IL-22) have been shown to play important roles in the pathogenesis of autoimmune diseases and inflammation [49,50]. Their biological role in the tumor microenvironment is poorly understood, and at present suggested to be both beneficial and detrimental to the cancer patient [51]. The generation and regulation of T H 17 cells in ovarian cancer have been documented [45] and the possible function and clinical relevance of these cells in human tumor microenvironments reported [46].…”

Section: Inflammatory Leukocytes In the Tumor Microenvironmentmentioning

confidence: 99%

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

Barnas

Simpson-Abelson

Yokota

et al. 2010

Cancer Microenvironment

View full text Add to dashboard Cite

The immune system of cancer patients recognizes tumor-associated antigens expressed on solid tumors and these antigens are able to induce tumor-specific humoral and cellular immune responses. Diverse immunotherapeutic strategies have been used in an attempt to enhance both antibody and T cell responses to tumors. While several tumor vaccination strategies significantly increase the number of tumor-specific lymphocytes in the blood of cancer patients, most vaccinated patients ultimately experience tumor progression. CD4+ and CD8+ T cells with an effector memory phenotype infiltrate human tumor microenvironments, but most are hyporesponsive to stimulation via the T cell receptor (TCR) and CD28 under conditions that activate memory T cells derived from the peripheral blood of the cancer patients or normal donors. Attempts to identify cells and molecules responsible for the TCR signaling arrest of tumor-infiltrating T cells have focused largely upon the immunosuppressive effects of tumor cells, tolerogenic dendritic cells and regulatory T cells. Here we review potential mechanisms by which human T cell function is arrested in the tumor microenvironment with a focus on the immunomodulatory effects of stromal fibroblasts. Determining in vivo which cells and molecules are responsible for the TCR arrest in human tumor-infiltrating T cells will be necessary to formulate and test strategies to prevent or reverse the signaling arrest of the human T cells in situ for a more effective design of tumor vaccines. These questions are now addressable using novel human xenograft models of tumor microenvironments.

show abstract

“…(4). The prevalence of Th17 cells was found to increase in the tumor microenvironment during tumor development (5). In addition, IL-17 plays a prominent role by increasing the angiogenic activity (6) via certain indirect mechanisms, such as (i) induction of IL-17-responsive cells to secrete proinflammatory cytokines, e.g., IL-6 and IL-1β, which also possess potent angiogenic activity (7); (ii) induction of a wide range of angiogenic mediators but inhibition of the angiostatic chemokine secretion (8); and (iii) induction of tumor and epithelial cells to secrete increasing levels of angiogenic chemokines (9).…”

mentioning

confidence: 99%

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Sung

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

486

386

View full text Add to dashboard Cite

The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotictreated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.H epatocellular carcinoma (HCC) is one of the most common cancers, the sixth most common neoplasm, and the second most deadly type of cancer worldwide (1). The traditional HCC treatment, including surgical treatment, local ablation therapy, and chemotherapy, could offer potential cure, yet patients are facing many limitations including the poor hepatic reserve. HCC is clearly a disease for which alternative therapeutic strategies must be developed. A better understanding of the interactions between cancer cells and stromal components in the tumorassociated proinflammatory microenvironment would be important for the management of this disease.The tumor microenvironment is infiltrated with various immune cells such as T cells, macrophages, neutrophils, natural killer (NK) cells, and myeloid-derived suppressor cells. Inflammation is known to play a pivotal role in tumor development by escalating tumor angiogenesis and cell growth. Once a solid tumor is formed, inflammation arises in the tumor-promoting direction. At the same time, new vasculature is needed in the tumor to provide nutrients and oxygen to support the growth of cancer cells, and this process plays a critical role in HCC, a highly vascularized tumor (2). Inflammation and angiogene...

show abstract

Protumor vs Antitumor Functions of IL-17

Cited by 322 publications

References 111 publications

Immunology of hepatocellular carcinoma

Immunology of hepatocellular carcinoma

T Cells and Stromal Fibroblasts in Human Tumor Microenvironments Represent Potential Therapeutic Targets

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Contact Info

Product

Resources

About