Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T‐Cells to Activation‐Induced Cell Death in Colorectal Cancer

Liu, Huashan; Liang, Zhenxing; Cheng, Sijing; Huang, Liang; Li, Wenxin; Zhou, Chi; Zheng, Xiaobin; Li, Shujuan; Zeng, Ziwei; Kang, Liang

doi:10.1002/advs.202203757

Cited by 19 publications

(9 citation statements)

References 47 publications

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“…These pathways can point that T-cell response and antigen presentation were reduced in KRAS-positive tissues, as described by Liu et al. ( 89 ).…”

Section: Discussionmentioning

confidence: 58%

Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing

Holubekova,

Loderer,

Grendar

et al. 2023

Front. Oncol.

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IntroductionColorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as driver mutations, gene methylations, etc., and influenced by tumor microenvironment (TME) pervaded with immune cells with both pro- and anti-tumor effects. The studying of interactions between the immune system (IS) and the TME is important for developing effective immunotherapeutic strategies for CRC. In our study, we focused on the analysis of expression profiles of inflammatory and immune-relevant genes to identify aberrant signaling pathways included in carcinogenesis, metastatic potential of tumors, and association of Kirsten rat sarcoma virus (KRAS) gene mutation.MethodsA total of 91 patients were enrolled in the study. Using NGS, differential gene expression analysis of 11 tumor samples and 11 matching non-tumor controls was carried out by applying a targeted RNA panel for inflammation and immunity genes containing 475 target genes. The obtained data were evaluated by the CLC Genomics Workbench and R library. The significantly differentially expressed genes (DEGs) were analyzed in Reactome GSA software, and some selected DEGs were used for real-time PCR validation.ResultsAfter prioritization, the most significant differences in gene expression were shown by the genes TNFRSF4, IRF7, IL6R, NR3CI, EIF2AK2, MIF, CCL5, TNFSF10, CCL20, CXCL11, RIPK2, and BLNK. Validation analyses on 91 samples showed a correlation between RNA-seq data and qPCR for TNFSF10, RIPK2, and BLNK gene expression. The top differently regulated signaling pathways between the studied groups (cancer vs. control, metastatic vs. primary CRC and KRAS positive and negative CRC) belong to immune system, signal transduction, disease, gene expression, DNA repair, and programmed cell death.ConclusionAnalyzed data suggest the changes at more levels of CRC carcinogenesis, including surface receptors of epithelial or immune cells, its signal transduction pathways, programmed cell death modifications, alterations in DNA repair machinery, and cell cycle control leading to uncontrolled proliferation. This study indicates only basic molecular pathways that enabled the formation of metastatic cancer stem cells and may contribute to clarifying the function of the IS in the TME of CRC. A precise identification of signaling pathways responsible for CRC may help in the selection of personalized pharmacological treatment.

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“…These pathways can point that T-cell response and antigen presentation were reduced in KRAS-positive tissues, as described by Liu et al. ( 89 ).…”

Section: Discussionmentioning

confidence: 58%

Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing

Holubekova,

Loderer,

Grendar

et al. 2023

Front. Oncol.

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“…In fact, immune checkpoints alone are not sufficient to predict the efficiency of the immunotherapy due to a highly complex immune tumor microenvironment, which could be generalized by a cancer immunity cycle (87). Several studies have suggested integrating multiple biomarkers to predict the immune response, including tumor-infiltrating lymphocytes, mutational b u r d e n , i m m u n e g e n e s i g n a t u r e s , a n d m u l t i p l e x immunohistochemistry (88,89). TIDE is a reliable surrogate biomarker that could accurately predict immune checkpoint blockade (ICB) response by measuring the tumor immune escape, and it even performed better than PD-L1 expression in melanoma; that is, a higher TIDE score is associated with worse ICB response and worse patient survival under anti-PD1 and anti-CTLA4 therapies (90).…”

Section: Discussionmentioning

confidence: 99%

Identifying Clinically Relevant Transcriptional Signatures and Methylation Profiles in the Course, Treatment and Outcome of Colorectal Cancer

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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“…We also explored MSI and LRHG signatures during the research process. The common mutation in GC is KRAS, which plays an important role in immunotherapy for solid tumors and colorectal cancer 46 , 47 . Whether there is a relationship between KRAS mutations and immunotherapy in GC patients remains unproven.…”

Section: Discussionmentioning

confidence: 99%

Bacterial lipopolysaccharide related genes signature as potential biomarker for prognosis and immune treatment in gastric cancer

Yuan,

Zhang,

et al. 2023

Sci Rep

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The composition of microbial microenvironment is an important factor affecting the development of tumor diseases. However, due to the limitations of current technological levels, we are still unable to fully study and elucidate the depth and breadth of the impact of microorganisms on tumors, especially whether microorganisms have an impact on cancer. Therefore, the purpose of this study is to conduct in-depth research on the role and mechanism of prostate microbiome in gastric cancer (GC) based on the related genes of bacterial lipopolysaccharide (LPS) by using bioinformatics methods. Through comparison in the Toxin Genomics Database (CTD), we can find and screen out the bacterial LPS related genes. In the study, Venn plots and lasso analysis were used to obtain differentially expressed LPS related hub genes (LRHG). Afterwards, in order to establish a prognostic risk score model and column chart in LRHG features, we used univariate and multivariate Cox regression analysis for modeling and composition. In addition, we also conducted in-depth research on the clinical role of immunotherapy with TMB, MSI, KRAS mutants, and TIDE scores. We screened 9 LRHGs in the database. We constructed a prognostic risk score and column chart based on LRHG, indicating that low risk scores have a protective effect on patients. We particularly found that low risk scores are beneficial for immunotherapy through TIDE score evaluation. Based on LPS related hub genes, we established a LRHG signature, which can help predict immunotherapy and prognosis for GC patients. Bacterial lipopolysaccharide related genes can also be biomarkers to predict progression free survival in GC patients.

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Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T‐Cells to Activation‐Induced Cell Death in Colorectal Cancer

Cited by 19 publications

References 47 publications

Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing

Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing

Identifying Clinically Relevant Transcriptional Signatures and Methylation Profiles in the Course, Treatment and Outcome of Colorectal Cancer

Bacterial lipopolysaccharide related genes signature as potential biomarker for prognosis and immune treatment in gastric cancer

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