J Exp Clin Canc Res
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J Exp Clin Canc Res · Sep 2021
Combinational blockade of MET and PD-L1 improves pancreatic cancer immunotherapeutic efficacy.
Dysregulated expression and activation of receptor tyrosine kinases (RTKs) are associated with a range of human cancers. However, current RTK-targeting strategies exert little effect on pancreatic cancer, a highly malignant tumor with complex immune microenvironment. Given that immunotherapy for pancreatic cancer still remains challenging, this study aimed to elucidate the prognostic role of RTKs in pancreatic tumors with different immunological backgrounds and investigate their targeting potential in pancreatic cancer immunotherapy. ⋯ This study systematically investigated the potential effectiveness of a novel pancreatic cancer immunotherapy targeting RTKs, and revealed the function of MET in PD-L1 regulation as well as the combined therapeutic efficacy of MET and PD-L1 in pancreatic cancer.
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J Exp Clin Canc Res · May 2021
ReviewWhat are the applications of single-cell RNA sequencing in cancer research: a systematic review.
Single-cell RNA sequencing (scRNA-seq) is a tool for studying gene expression at the single-cell level that has been widely used due to its unprecedented high resolution. In the present review, we outline the preparation process and sequencing platforms for the scRNA-seq analysis of solid tumor specimens and discuss the main steps and methods used during data analysis, including quality control, batch-effect correction, normalization, cell cycle phase assignment, clustering, cell trajectory and pseudo-time reconstruction, differential expression analysis and gene set enrichment analysis, as well as gene regulatory network inference. ⋯ In the second part of this review, we focus on the application of scRNA-seq in solid tumors, and summarize the findings and achievements in tumor research afforded by its use. ScRNA-seq holds promise for improving our understanding of the molecular characteristics of cancer, and potentially contributing to improved diagnosis, prognosis, and therapeutics.
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AS (alternative splicing) is a fundamental process by which a gene can generate multiple distinct mRNA transcripts to increase protein diversity. Defects in AS influence the occurrence and development of many diseases, including cancers, and are frequently found to participate in various aspects of cancer biology, such as promoting invasion, metastasis, apoptosis resistance and drug resistance. NcRNAs (noncoding RNAs) are an abundant class of RNAs that do not encode proteins. ⋯ NcRNAs can directly or indirectly influence a plethora of molecular targets to regulate cis-acting elements, trans-acting factors, or pre-mRNA transcription at multiple levels, affecting the AS process and generating alternatively spliced isoforms. Consequently, ncRNA-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. In this review, we summarize the current mechanisms by which ncRNAs regulate AS in cancers and discuss their potential clinical applications as biomarkers and therapeutic targets.
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J Exp Clin Canc Res · Jan 2021
Promotion of epithelial-mesenchymal transformation by hepatocellular carcinoma-educated macrophages through Wnt2b/β-catenin/c-Myc signaling and reprogramming glycolysis.
Tumour-associated macrophages (TAMs) in the tumour microenvironment (TME) can promote the progression of hepatocellular carcinoma (HCC). Some tumours can be suppressed by targeting Wnt2b in tumour cells. However, the role of Wnt2b in HCC is still unknown. In particular, the role of Wnt2b-mediated signal activation in macrophage polarization in the HCC microenvironment, and the regulatory effect between Wnt and glycolysis in TAMs has not been described. ⋯ As a potential target for HCC therapy, Wnt2b may play an important regulatory role for the functions of TAMs in the TME. Moreover, the TLR9 agonist CpG ODN might act as a Wnt2b signal inhibitor and can potentially be employed for HCC therapy by disturbing Wnt2b/β-catenin/c-Myc and inhibiting glycolysis in HCC-TAMs.
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J Exp Clin Canc Res · Nov 2020
Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis.
Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC). ⋯ Evodiamine can suppress NSCLC by elevating of CD8+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma.