Tumor cell-expressed IL-15Rα drives antagonistic effects on the progression and immune control of gastric cancer and is epigenetically regulated in EBV-positive gastric cancer

Wei, Jing; Guo, Cheng; An, Xiang; Miao, Wenxuan; Zhang, Chen-Li; Wang, Binsheng; Cai, Wei; Li, Min; Zhang, Fangfang

doi:10.1007/s13402-020-00542-4

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…For example, the expression of TRIM22 was increased during T lymphocyte activation with IL-15 ( 35 ). In tumor, IL-15 was associated with lymphocyte infiltration in the micro-environment ( 36 ), and we might speculate that TRIM22 mediated this process and further exploration awaits.…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

et al. 2022

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Given the importance of tripartite motif (TRIM) proteins in diverse cellular biological processes and that their dysregulation contributes to cancer progression, we constructed a robust TRIM family signature to stratify patients with kidney renal clear cell carcinoma (KIRC). Transcriptomic profiles and corresponding clinical information of KIRC patients were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. Prognosis-related TRIM family genes were screened and used to construct a novel TRIM family-based signature for the training cohort. The accuracy and generalizability of the prognostic signature were assessed in testing, entire, and external ICGC cohorts. We analyzed correlations among prognostic signatures, tumor immune microenvironment, and immune cell infiltration. The results of univariate Cox regression and Kaplan-Meier survival analyses revealed 27 TRIMs that were robustly associated with the prognosis of patients with KIRC. We applied Lasso regression and multivariate Cox regression analyses to develop a prognostic signature containing the TRIM1, 13, 35, 26, 55, 2, 47, and 27 genes to predict the survival of patients with KIRC. The accuracy and generalizability of this signature were confirmed in internal and external validation cohorts. We also constructed a predictive nomogram based on the signature and the clinicopathological characteristics of sex, age, and T and M status to aid clinical decision-making. We analyzed immune cell infiltration analysis and found that CD8 T cells, memory resting CD4 T cells, and M2 macrophages were the most enriched components in the KIRC tumor immune microenvironment. A higher level of immune infiltration by plasma cells, follicular helper T cells, and activated NK cells, and a lower level of immune infiltration by memory resting CD4 T cells, M1 and M2 macrophages, and resting dendritic cells were associated with higher risk scores. Overall, our eight-gene TRIM family signature has sufficient accuracy and generalizability for predicting the overall survival of patients with KIRC. Furthermore, this prognostic signature is associated with tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

et al. 2022

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“…However, the difference was not statistically signi cant and additional samples have to be collected for further analysis. [15][16][17] . The present study indicated that EBV positive and negative gastric cancer cases did not reveal signi cant differences with regard to gender (P = 0.844), age (P = 0.9355), gross classi cation (P = 0.844), Lauren classi cation (P = 0.96), histological grade (P = 0.149), early and advanced gastric cancer stage (P = 0.665), vascular invasion (P = 0.426), nerve invasion (P = 0.802), T stage (P = 0.776), N stage (P = 0.499), M stage (P = 0.306), survival status (survival or death) (P = 0.843), maximum tumor diameter (P = 0.446) and number of lymph node metastasis (P = 0.466).…”

Section: Discussionmentioning

confidence: 99%

“…Wild-type P53 inhibits tumor progression. However, following P53 mutation, this transcription factor loses its ability to suppress cell proliferation 17,23,27,28 . In the current study, mutant P53 expression was detected.…”

Section: Discussionmentioning

confidence: 99%

The Association of EBV and Gastric Cancer

Wang

Tian

Yu³

et al. 2021

Preprint

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The present study aimed to investigate the clinicopathological features of EBV positive and EBV negative gastric cancer patients and the expression levels of proliferative, apoptotic and cell signaling proteins in tissues samples from these patients. The biological role of EBV infection was assessed in gastric cancer. Results: EBV was localized in the nuclei of gastric cancer cells (positive rate 6.86%). The infection rate of EBV in normal gastric mucosal cells, which were adjacent to cancer tissues, was 0. The difference noted was significant (P = 0. 023). The expression levels of caspase-3 (P = 0.0423), FASL (P = 0.00297) and cyclin D1 (P = 0.0345) proteins were significantly different in EBV positive and negative gastric cancer tissues. When the parameters gender, age, Lauren classification, histological grade, early and advanced tumor stage, vascular and nerve invasion, TNM grade and survival status were compared, the maximum tumor diameter, number of lymph node metastasis, caspase-8, Ki67 and P53 protein expression did not reveal significant differences. Bcl-2 protein expression was positive in only one gastric cancer cell sample and negative in the other gastric cancer cell samples as well as in the corresponding normal gastric mucosal epithelial cells. However, significant differences were noted with regard to the positive expression of Bcl-2 in the immune cells of gastric cancer and adjacent tissues (P = 1.17749E-39). The expression levels of Bcl-2 in the immune cells of EBV positive and EBV negative gastric cancer tissues were not significantly different. The expression levels of caspase-8, caspase-3, FASL, Ki67, cyclin D1 and P53 proteins in gastric cancer cells were significantly different compared to those of normal gastric mucosal cells derived from adjacent tissues (P < 0.05). These findings were noted in both EBV positive and/or EBV negative gastric cancer cases (P < 0.05). The survival time of the patients with EBV positive gastric cancer was higher than that of the patients with EBV negative gastric cancer, whereas the differences were not significantly different. The aforementioned results suggested that the EBV virus may directly infect cancerous cells but not normal gastric mucosal cells. With the exception of caspase-3, the expression levels of the proteins FASL and cyclin D1 were closely associated with EBV-positive gastric cancer. EBV did not have a specific effect on the expression of the signaling molecules associated with proliferation and apoptosis of gastric cancer cells. Its effect on gastric cancer cells may be associated with other factors and requires further discussion. No significant differences were noted in the clinicopathological features of EBV positive compared to those of EBV negative gastric cancer patients. However, the prognosis of EBV positive gastric cancer patients was better than that of EBV negative gastric cancer patients. The mechanism of action associated with these processes requires further verification.

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“…In the case of EBV-positive GC, cells expressed the interleukin IL-15Rα receptor binds to IL 15 and allows the increase of natural killer cells, in addition to the regulation of the JAK/STAT pathway and thyrosine kinase pathways such as MAPK and PI3K ( 70 ), at a lower level than EBV-negative cells due to promoter hypermethylation ( 43 ); therefore, administration of IL-15 to stimulate immune responses against cancer could be a promising strategy in GC.…”

Section: Epigenetic Modulations Of Cytokines In Gcmentioning

confidence: 99%

Epigenetic modulation of cytokine expression in gastric cancer: influence on angiogenesis, metastasis and chemoresistance

Reyes,

Pulgar,

Vivallo

et al. 2024

Front. Immunol.

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Cytokines are proteins that act in the immune response and inflammation and have been associated with the development of some types of cancer, such as gastric cancer (GC). GC is a malignant neoplasm that ranks fifth in incidence and third in cancer-related mortality worldwide, making it a major public health issue. Recent studies have focused on the role these cytokines may play in GC associated with angiogenesis, metastasis, and chemoresistance, which are key factors that can affect carcinogenesis and tumor progression, quality, and patient survival. These inflammatory mediators can be regulated by epigenetic modifications such as DNA methylation, histone protein modification, and non-coding RNA, which results in the silencing or overexpression of key genes in GC, presenting different targets of action, either direct or mediated by modifications in key genes of cytokine-related signaling pathways. This review seeks insight into the relationship between cytokine-associated epigenetic regulation and its potential effects on the different stages of development and chemoresistance in GC.

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Tumor cell-expressed IL-15Rα drives antagonistic effects on the progression and immune control of gastric cancer and is epigenetically regulated in EBV-positive gastric cancer

Cited by 6 publications

References 46 publications

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

The Association of EBV and Gastric Cancer

Epigenetic modulation of cytokine expression in gastric cancer: influence on angiogenesis, metastasis and chemoresistance

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