Expression of Th17/Treg related molecules in gastric cancer tissues

Zhu, Shoumin; Dong, Qi; Zhang, Shutian; Zhou, Chunxiang

doi:10.5152/tjg.2018.17114

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…AIG in its late stage is characterized by intestinal metaplasia, gastric corpus and fundus dysplasia, and chromaffin cell hyperplasia that are considered precursor lesions of gastric cancer, suggesting an important link between AIG and gastric cancer (29). Ample scientific evidence indicates that gastric Th17 responses were associated with gastric adenocarcinoma and promoted gastric oncogenesis (13,14,(30)(31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Bella

Antico²,

Panozzo³

et al. 2022

Front. Immunol.

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Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+/K+-adenosine triphosphatase (H+/K+-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+/K+-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+/K+-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+/K+-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+/K+-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.

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Section: Discussionmentioning

confidence: 99%

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Bella

Antico²,

Panozzo³

et al. 2022

Front. Immunol.

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“…IL17 and IL-6 have been associated with tumor progression, and Foxp3 and TGF-β1 were mainly expressed in patients with advanced gastric cancer. These findings suggest that these molecules play a role in the tumor immune response evasion and cancer progression[ 144 ].…”

Section: Association Between Th17 Response and Different Types Of Cancermentioning

confidence: 99%

Relationship between Th17 immune response and cancer

Marques¹,

Brito²,

Silva³

et al. 2021

WJCO

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Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades. Cancer has a close relationship with the immune system and, although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity, studies have emphasized their roles in cancer pathogenesis. The Th17 immune response profile is involved in several types of cancer including urogenital, respiratory, gastrointestinal, and skin cancers. This type of immune response exerts pro and antitumor functions through several mechanisms, depending on the context of each tumor, including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment. Among other factors, the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential, which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells. Interleukin (IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment, which allow Th17 cells to prevail in tumors. Moreover, the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers, being associated with variable clinical outcomes. The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

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“…According to the previous data, the accumulation of Th17 and Treg cells in the gastric tumor microenvironment is associated with the clinical stage and leads to an imbalanced Th17/Treg in patients with advanced gastric cancer [ 8 – 10 ]. These studies demonstrated the distribution of Th17 cells in relation to Treg in peripheral blood, tumor-draining lymph nodes, and tumor tissues of patients with gastric cancer compared to healthy individuals [ 10 , 11 ]. IL-6 and TGF- β induce Th17 differentiation either in normal condition [ 12 , 13 ] or in gastric cancer that it leads to an imbalanced Th17/Treg.…”

Section: Introductionmentioning

confidence: 99%

Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells

Rezalotfi

Solgi

Ebrahimi

2020

Journal of Immunology Research

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Background. Gastrosphere, an enriched cellular population with stem-like properties believed to be responsible for an escape from immune-mediated destruction. Th17 and Treg cells play a major role in gastric cancer; however, their interaction with gastrospheres remained elusive. Method. Peripheral blood mononuclear cells were isolated from healthy donors and were cultured with conditioned media of MKN-45 (parental) cells as well as gastrospheres’ conditioned media in the context of mixed lymphocyte reaction and in the presence of anti-CD3/CD28 beads. The proliferation was evaluated using CFSE staining; the percentages of CD4+CD25+FoxP3+ Treg and CD4+IL-17+ Th17 cells and IFN-γ+cells and the production of IL-17, TGF-β, and IL-10 were assessed by flow cytometry and ELISA, respectively. Finally, the cytotoxic potential of induced immune cells was measured by examining the secretion of lactate dehydrogenase from target cells. Results. The results revealed a decreased expansion of PBMCs postexposure to gastrospheres’ conditioned medium which was concomitant with an increased percentage of Th17 and an enhanced Th17 to Treg ratio. The conditioned media of gastrospheres enhanced the secretion of IL-10 and IL-17 and decreased TGF-β. Interestingly, immune cells induced by gastrospheres showed significant cytotoxicity in terms of producing IFN-γ and death induction in target cells. All these changes were related to the upregulation of IL-6, IL-10, and IL-22 in gastrospheres compared to parental cells. Conclusion. Our study showed that the condition media of gastrospheres can potentially induce Th17 with increasing in their cytotoxic effect. Based on our knowledge, the present study is the first study that emphasizes the role of gastrospheres in the induction of antitumor Th17 cells. However, it should be confirmed with complementary studies in vivo.

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Expression of Th17/Treg related molecules in gastric cancer tissues

Abstract: Background/Aims: The function of regulatory T cells (Treg) and helper T cells 17 (Th17) related indexes, such as interleukin (IL)-

Cited by 12 publications

References 31 publications

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity

Relationship between Th17 immune response and cancer

Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells

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