Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma

Holderried, Tobias A. W.; Vos, Luka de; Bawden, Emma Grace; Vogt, Timo; Dietrich, Jörn; Zarbl, Romina; Bootz, Friedrich; Kristiansen, Glen; Brossart, Peter; Landsberg, Jennifer; Dietrich, Dimo

doi:10.1186/s13148-019-0752-8

Cited by 54 publications

(45 citation statements)

References 73 publications

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“…Interestingly, regarding the relationship between TIM-3 and GC prognosis, we found that high expression of TIM-3 shows a favorable prognosis. This result is consistent with Holderried et al's research [ 43 ]. Besides, we found that TIGIT expression decreases in patients who received targeted therapy.…”

Section: Discussionsupporting

confidence: 94%

Immune Cell Landscape in Gastric Cancer

Yang

Wang

et al. 2021

BioMed Research International

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Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

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Section: Discussionsupporting

confidence: 94%

Immune Cell Landscape in Gastric Cancer

Yang

Wang

et al. 2021

BioMed Research International

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“…This gene is responsible for suppressing T-cell proliferation, inducing T-cell apoptosis, and associated with angiogenesis and cytokine signaling. Activation results in autocrine release of Gal9, and is linked to inducing apoptosis [31]. This is supported in our apoptosis tests (Figure 6), where a statistically significant increase of late apoptosis was observed in InP/ZnS-treated cells compared to NTC.…”

Section: Upregulated Gene Processes Induce Apoptosis and Inhibit Metasupporting

confidence: 82%

“…Immune function was also observed by Holderried et al by investigation of T cell-mediated tumor evasion. Galactin-9, a ligand made by LGALS9, was upregulated in colorectal tumors and hypothesized to be a therapeutic target for immune-mediated anti-cancer therapies [31]. Collectively, we suggest cellular stress could activate the immune system in the presence of InP/ZnS QDs and induce apoptosis in tumor cells (Figure 9a).…”

Section: Upregulated Gene Processes Induce Apoptosis and Inhibit Metamentioning

confidence: 86%

An Assessment of InP/ZnS as Potential Anti-Cancer Therapy: Quantum Dot Treatment Increases Apoptosis in HeLa Cells

Davenport

Horstmann

Patel

et al. 2021

JNT

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InP/ZnS quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anticancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QD-treated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. RT-qPCR assay was performed to confirm the findings of transcriptome analysis, and the QD mode of action was illustrated. Our study determined both IC50 concentration of 69 µg/mL and MIC concentration of 167 µg/mL of InP/ZnS. It was observed via XTT assay that cell viability was decreased significantly at the MIC. Production of superoxide, measured by ROS assay with flow cytometry, was decreased, whereas levels of nitrogen radicals increased. Using analysis of apoptosis, we found that induced cell death in the QD-treated samples was shown to be significantly increased when compared to untreated cells. We conclude InP/ZnS QD to decrease cell viability by inducing stress via ROS levels, apoptosis induction, and alteration of transcriptome.

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“…Transmembrane receptor TIM-3 was encoded by HAVCR2 and expressed on a variety of cells [ 42 ]. The expression of TIM-3 is closely related to exhaustion and impaired function of T cells.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Immunoinhibitors Identifies LGALS9 and TGFBR1 as Potential Prognostic Biomarkers for Pancreatic Cancer

Fan

et al. 2020

Computational and Mathematical Methods in Medicine

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Pancreatic cancer (PC) is one of the most deadly cancers worldwide. To uncover the unknown novel biomarker used to indicate early diagnosis and prognosis in the molecular therapeutic field of PC is extremely of importance. Accumulative evidences indicated that aberrant expression or activation of immunoinhibitors is a common phenomenon in malignances, and significant associations have been noted between immunoinhibitors and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of immunoinhibitors contributing to tumorigenesis and progression of pancreatic cancer (PC) have not yet been elucidated clearly. In this study, we investigated the distinct expression and prognostic value of immunoinhibitors in patients with PC by analyzing a series of databases, including TISIDB, GEPIA, cBioPortal, and Kaplan-Meier plotter database. The mRNA expression levels of IDO1, CSF1R, VTCN1, KDR, LGALS9, TGFBR1, TGFB1, IL10RB, and PVRL2 were found to be significantly upregulated in patients with PC. Aberrant expression of TGFBR1, VTCN1, and LGALS9 was found to be associated with the worse outcomes of patients with PC. Bioinformatics analysis demonstrated that LGALS9 was involved in regulating the type I interferon signaling pathway, interferon-gamma-mediated signaling pathway, RIG-I-like receptor signaling pathway, NF-kappa B signaling pathway, cytosolic DNA-sensing pathway, and TNF signaling pathway. And TGFB1 was related to mesoderm formation, cell matrix adhesion, TGF-beta signaling pathway, and Hippo signaling pathway. These results suggested that LGALS9 and TGFBR1 might serve as potential prognostic biomarkers and targets for PC.

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Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma

Cited by 54 publications

References 73 publications

Immune Cell Landscape in Gastric Cancer

Immune Cell Landscape in Gastric Cancer

An Assessment of InP/ZnS as Potential Anti-Cancer Therapy: Quantum Dot Treatment Increases Apoptosis in HeLa Cells

Comprehensive Analysis of Immunoinhibitors Identifies LGALS9 and TGFBR1 as Potential Prognostic Biomarkers for Pancreatic Cancer

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