LINC00152 mediates CD8+ T-cell infiltration in gastric cancer through binding to EZH2 and regulating the CXCL9, 10/CXCR3 axis

Ou, Jinqing; Lei, Pingguang; Yang, Zehua; Yang, Man; Luo, Ling-Min; Mo, Hongdan; Luo, Guijin; He, Junhui

doi:10.1007/s10735-021-09967-z

Cited by 22 publications

(12 citation statements)

References 30 publications

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“…Although the above studies showed that immunotherapy has a good therapeutic effect on patients, the therapeutic effect of immunotherapy varies in different patients. Currently, it is believed that the effect of tumor immunotherapy is greatly affected by immune escape of tumor cells [ 7 ]. CD8+T cells infiltrated by tumor are the main effect or cells mediating anti-tumor immune response [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration

Lin

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. lncRNAs affect adaptive and innate immunity of cancer via mediating functional states of immune cells, genes, and pathways. Nonetheless, little is known about the molecular mechanism of lncRNA-mediated CD8+ T cell immune infiltration in progression of clear cell renal cell carcinoma (ccRCC). We designed this work to investigate the role of LINC00887 in regulating CD8+ T cell immune infiltration in ccRCC. Methods. Correlation between LINC00887 and immune factors and the expression level of LINC00887 in ccRCC were analyzed by bioinformatics methods (TCGA-KIRC database, “edgeR” package, “clusterProfiler” package, and “CIBERSORT” package). LINC00887 expression in ccRCC was examined via RT-qPCR. The cytokilling capacity of CD8+ T cells was evaluated by the lactate dehydrogenase assay. The apoptotic ability of CD8+ T cells was measured by flow cytometry. The chemotactic ability of CD8+ T cells was revealed by chemotaxis assay. CXCR3, CXCL9, and CXCL10 levels were assessed by RT-qPCR. Results. As suggested by bioinformatics analysis, LINC00887 was markedly upregulated in ccRCC patients and associated with expression of immune-suppression molecule, thereby abating the immune infiltration level of CD8+ cells in tumor tissue. As revealed by cellular assay, LINC00887 was upregulated in ccRCC cells, and knockdown of LINC00887 resulted in a decreased PD-L1 expression, increased CD8+ T cell toxicity, decreased apoptotic levels, and enhanced chemotaxis. Moreover, we found that LINC00887 exhibited inhibitory effect on immune infiltration of CD8+ cells in clinical tissues. Conclusions. The results of this study suggested that LINC00887 promoted ccRCC progression by inhibiting immune infiltration of CD8+ T cells, providing new insights into pathogenesis of ccRCC and suggesting LINC00887 being a promising immunotherapy target for ccRCC.

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Section: Introductionmentioning

confidence: 99%

LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration

Lin

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Many abnormally expressed lncRNAs have been recognized in GC tissues, which affect the occurrence and prognosis of tumors ( Table 1 ). Moreover, lncRNA regulate immunity in several ways in GC through influencing the polarization of GC-associated macrophages ( Xie et al, 2020 ), the differentiation of natural killer cells ( Ou et al, 2021 ), the regulation of dendritic cells ( Demaria et al, 2019 ) and so on ( Xiao et al, 2022b ).…”

Section: Lncrnas and The Mechanism Of Immunotherapy Resistance In Gcmentioning

confidence: 99%

LncRNA and its role in gastric cancer immunotherapy

Zhang

Wang

Yang³

et al. 2023

Front. Cell Dev. Biol.

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Gastric cancer (GC) is a potential dominant disease in tumor immunotherapy checkpoint inhibitors, and adoptive cell therapy have brought great hope to GC patients. However, only some patients with GC can benefit from immunotherapy, and some patients develop drug resistance. More and more studies have shown that long non-coding RNAs (lncRNAs) may be important in GC immunotherapy’s prognosis and drug resistance. Here, we summarize the differential expression of lncRNAs in GC and their impact on the curative effect of GC immunotherapy, discuss potential mechanisms of activity in GC immunotherapy resistance regulated by lncRNAs. This paper reviews the differential expression of lncRNA in GC and its effect on immunotherapy efficacy in GC. In terms of genomic stability, inhibitory immune checkpoint molecular expression, the cross-talk between lncRNA and immune-related characteristics of GC was summarized, including tumor mutation burden (TMB), microsatellite instability (MSI), and Programmed death 1 (PD-1). At the same time, this paper reviewed the mechanism of tumor-induced antigen presentation and upregulation of immunosuppressive factors, as well as the association between Fas system and lncRNA, immune microenvironment (TIME) and lncRNA, and summarized the functional role of lncRNA in tumor immune evasion and immunotherapy resistance.

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“…M1-polarized TAM-derived exosomes can down-regulate the expression of PD-L1 in gastric cancer cells through miR-16-5p and activate T cell immunity ( 115 ). Linc00152 inhibits CD8 + T cell infiltration in GC by binding to enhancer of zeste homolog 2 (EZH2) and regulating the CXCL9, 10/CXCR3 axis ( 116 ).…”

Section: Noncoding Rnas and Exosomes In Gc Tmementioning

confidence: 99%

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

Liu

et al. 2022

Front. Immunol.

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Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor function. As the tumor progresses, tumor immune tolerance is induced under the action of various factors, such that the tumor suppressor microenvironment is continuously transformed into a tumor-promoting microenvironment, which promotes tumor immune escape. Eventually, tumor cells manifest the characteristics of malignant proliferation, invasion, metastasis, and drug resistance. In recent years, stress effects of the extracellular matrix, metabolic and phenotypic changes of innate immune cells (such as neutrophils, mast cells), and adaptive immune cells in the tumor microenvironment have been revealed to mediate the emerging mechanisms of immune tolerance, providing us with a large number of emerging therapeutic targets to relieve tumor immune tolerance. Gastric cancer is one of the most common digestive tract malignancies worldwide, whose mortality rate remains high. According to latest guidelines, the first-line chemotherapy of advanced gastric cancer is the traditional platinum and fluorouracil therapy, while immunotherapy for gastric cancer is extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) and programmed death ligand 1 (PD-L1) targeted drugs, whose benefits are limited. Clinical experiments confirmed that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor receptor (VEGFR) and other targeted drugs alone or in combination with other drugs have limited efficacy in patients with advanced gastric cancer, far less than in lung cancer, colon cancer, and other tumors. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the immune tolerance of tumors is key to the success of gastric cancer immunotherapy. In this study, we summarize the latest mechanisms of various components of the tumor microenvironment in gastric cancer for inducing immune tolerance and promoting the formation of the malignant phenotype of gastric cancer, as well as the research progress of targeting the tumor microenvironment to overcome immune tolerance in the treatment of gastric cancer.

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LINC00152 mediates CD8+ T-cell infiltration in gastric cancer through binding to EZH2 and regulating the CXCL9, 10/CXCR3 axis

Cited by 22 publications

References 30 publications

LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration

LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration

LncRNA and its role in gastric cancer immunotherapy

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

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