Immune modulatory effects of oncogenic KRAS in cancer

Hamarsheh, Shaima’a; Groß, Olaf; Brummer, Tilman; Zeiser, Robert

doi:10.1038/s41467-020-19288-6

Cited by 238 publications

(223 citation statements)

References 96 publications

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“…Additionally, several types of tumor-infiltrating immune cells were notably related to the prognosis of HCC patients. 71 , 72 , 73 , 74 , 75 Furthermore, significant positive correlations were revealed between TAOK1 expression and some immune marker sets in dendritic cells, Th cells (Th1, Th2, and Th17) and Tregs in HCC. These findings together suggest that these differences induced by the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC.…”

Section: Discussionmentioning

confidence: 92%

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma

Shi

Zhang

Liu

et al. 2021

Molecular Therapy - Nucleic Acids

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Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA (ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.

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Section: Discussionmentioning

confidence: 92%

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma

Shi

Zhang

Liu

et al. 2021

Molecular Therapy - Nucleic Acids

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“…Cancers engage various immune escape mechanisms that can be dependent on specific tumor intrinsic factors. In fact, alterations in tumor suppressor PTEN; Liver Kinase B1 (LKB1); or oncogenes WNT/β-catenin, KRAS, or basic leucine zipper transcriptional factor ATF-like 3 (BATF3), affect effector T-cell recruitment to the tumors [ 121 , 122 , 123 , 124 , 125 ]. On the contrary, tumor hyper-activation of FAK leads to a recruitment of T reg cells, together with chemokine-driven CD8+ T cell exhaustion or poor infiltration within the tumor [ 126 , 127 ].…”

Section: Regulatory T Cells and Anticancer Immunitymentioning

confidence: 99%

CTLA-4 in Regulatory T Cells for Cancer Immunotherapy

Sobhani

Tardiel-Cyril

Davtyan

et al. 2021

Cancers

142

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Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are currently limited to a minority of patients and there is a need to develop a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind to CD80 and CD86 with a higher affinity than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of the ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap.

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“…These mutations prevent the hydrolysis of GTP to GDP, which disables the "off switch", constitutively activating KRAS regulated signaling pathways that drive tumor growth [85]. There is also evidence that KRAS mutations are involved in tumor cell evasion of host immune responses [86]. Similar to c-MYC, KRAS was considered impossible to target for many years.…”

Section: Krasmentioning

confidence: 99%

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

Brown

Kendrick

2021

Pharmaceuticals

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Stretches of cytosine-rich DNA are capable of adopting a dynamic secondary structure, the i-motif. When within promoter regions, the i-motif has the potential to act as a molecular switch for controlling gene expression. However, i-motif structures in genomic areas of repetitive nucleotide sequences may play a role in facilitating or hindering expansion of these DNA elements. Despite research on the i-motif trailing behind the complementary G-quadruplex structure, recent discoveries including the identification of a specific i-motif antibody are pushing this field forward. This perspective reviews initial and current work characterizing the i-motif and providing insight into the biological function of this DNA structure, with a focus on how the i-motif can serve as a molecular target for developing new therapeutic approaches to modulate gene expression and extension of repetitive DNA.

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Immune modulatory effects of oncogenic KRAS in cancer

Cited by 238 publications

References 96 publications

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma

CTLA-4 in Regulatory T Cells for Cancer Immunotherapy

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

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