Cholangiocarcinoma — novel biological insights and therapeutic strategies

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(7), P. 470 - 486

Published: May 15, 2023

Language: Английский

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Immunology and immunotherapy of cholangiocarcinoma

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(6), P. 349 - 365

Published: Jan. 25, 2023

Language: Английский

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Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 7, 2024

Abstract Colorectal cancer (CRC) remains one of the leading causes cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis CRC a testament to dysregulation these signaling cascades, which culminates in malignant transformation colonic epithelium. This review aims dissect foundational mechanisms implicated CRC, elucidate generalized principles underpinning neoplastic evolution progression. We discuss molecular hallmarks including genomic, epigenomic microbial features highlight role orchestration tumorigenic process. Concurrently, we advent targeted immune therapies assessing their impact on current clinical landscape. development has been informed deepening understanding oncogenic signaling, identification key nodes within can be exploited pharmacologically. Furthermore, explore potential integrating AI enhance precision therapeutic targeting patient stratification, emphasizing personalized medicine. In summary, our captures dynamic interplay between aberrant concerted efforts counteract changes through strategies, ultimately aiming pave way for improved prognosis treatment modalities colorectal cancer.

Language: Английский

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Pan‐Cancer Single‐Cell and Spatial‐Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 3, 2024

Abstract The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore impact APOE + on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. scRNA‐seq bulk RNA‐seq data are Integrated construct an M.Sig model for predicting based distinct molecular signatures macrophage algorithms. Comprehensive analysis as well in vivo vitro experiments applied potential mechanisms affecting response. shows clear advantages efficacy prognosis pan‐cancer patients. proportion is higher non‐responders triple‐negative breast cancer compared with responders, interaction longer distance between CD8 exhausted T (Tex) cells confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, combined treatment best efficacy. real‐world immunotherapy accurately predicts pan‐cancer, which may be associated Tex cells.

Language: Английский

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A multiomics analysis-assisted deep learning model identifies a macrophage-oriented module as a potential therapeutic target in colorectal cancer

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(2), P. 101399 - 101399

Published: Feb. 1, 2024

Colorectal cancer (CRC) is a common malignancy involving multiple cellular components. The CRC tumor microenvironment (TME) has been characterized well at single-cell resolution. However, spatial interaction map of the TME still elusive. Here, we integrate multiomics analyses and establish to improve prognosis, prediction, therapeutic development for CRC. We construct immune module (CCIM) that comprises FOLR2+ macrophages, exhausted CD8+ T cells, tolerant CD4+ regulatory cells. Multiplex immunohistochemistry performed depict CCIM. Based on this, utilize advanced deep learning technology predict chemotherapy response. CCIM-Net constructed, which demonstrates good predictive performance response in both training testing cohorts. Lastly, targeting macrophage therapeutics used disrupt immunosuppressive CCIM enhance vivo.

Language: Английский

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Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 12, 2024

Abstract Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify complex rare cell populations at single-cell resolution. By scRNA-seq, heterogeneity of tumor microenvironment across cervical carcinogenesis has mapped described. Whether these alterations could be detected applied to unclear. Herein, we performed scRNA-seq 56,173 exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade (HSIL), The present study delineated alteration immune epithelial derived during progression. A subset lipid-associated macrophage was identified as tumor-promoting element serve biomarker for predicting progression LSIL into HSIL, which then verified by immunofluorescence. Furthermore, cell–cell communication analysis indicated SPP1-CD44 axis might exhibit protumor interaction between macrophage. In this study, investigated multicellular ecosystem in potential biomarkers early detection.

Language: Английский

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Brain gliomas new transcriptomic discoveries from differentially expressed genes to therapeutic targets

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 20, 2025

Gliomas are a prevalent form of primary malignant brain tumor, yet the intricate molecular mechanisms underlying its pathogenesis remain unclear. This study aimed to identify new genetic targets linked glioma by analyzing microarray datasets uncover factors involved in onset and progression. We obtained two independent from Gene Expression Omnibus database, processed normalized them using R software, evaluated relationship between differentially expressed genes differential expression, expression quantitative trait loci, Mendelian randomization (MR) analyses. set enrichment analysis immunocytometric further explored biological functions pathways identified genes, which were validated The Cancer Genome Atlas Genotype-Tissue datasets. eight co-expressed genes—C1QB, GPX3, LRRC8B, TRIOBP, SNAPC5, SPI1, TSPYL5, FBXL16—that crucial various processes. CIBERSORT revealed significant immune cell-type distributions within gliomas, underscoring significance cell infiltration. Validation additional confirmed MR results upstream regulatory NetworkAnalyst. Our findings offer fresh perspectives on underpinnings highlight potential for therapeutic interventions.

Language: Английский

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An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(10), P. 2248 - 2269

Published: July 24, 2023

KRAS mutations are causally linked to protumor inflammation and identified as driving factors in tumorigenesis. Here, using multiomics data gathered from a large set of patients, we showed that mutation was associated with specific landscape alternative mRNA splicing connected myeloid intrahepatic cholangiocarcinoma (iCCA). Then, negative feedback mechanism which the upregulation interleukin 1 receptor antagonist (IL1RN)-201/203 due confers vital anti-inflammatory effects KRAS-mutant iCCA. In iCCA mice, both IL1RN-201/203 anakinra treatment ignited significant antitumor immune response by altering neutrophil recruitment phenotypes. Furthermore, synergistically enhanced anti-PD-1 therapy activate intratumoral GZMB+ CD8+ T cells mice. Clinically, found high levels patients were significantly superior immunotherapy. This work describes novel inflammatory checkpoint mediated IL1RN variants may serve promising basis develop therapeutic options for other cancers. article is featured Selected Articles Issue, p. 2109.

Language: Английский

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Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Nov. 8, 2023

Abstract Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as benefit only available for a fraction patients. A lack understanding CAR-T behaviors vivo at the single-cell level impedes their more extensive application practice. Mounting evidence suggests that sequencing techniques can help perfect design, guide gene-based T modification, and optimize manufacturing conditions, all them are essential long-term immunosurveillance favorable outcomes. The information generated by employing these methods also potentially informs our numerous complex factors dictate therapeutic efficacy toxicities. In this review, we discuss reasons why immunotherapy fails practice what field has learned since milestone technologies. We further outline recent advances analyses immunotherapy. Specifically, provide an overview studies focusing on target antigens, CAR-transgene integration, preclinical research applications, then how it will affect future therapy.

Language: Английский

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A cuproptosis-related gene expression signature predicting clinical prognosis and immune responses in intrahepatic cholangiocarcinoma detected by single-cell RNA sequence analysis

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 2, 2024

Abstract Background Cholangiocarcinoma represents a malignant neoplasm originating from the hepatobiliary tree, with subset of tumors developing inside liver. Intrahepatic cholangiocarcinomas (ICC) commonly exhibit an asymptomatic presentation, rendering both diagnosis and treatment challenging. Cuproptosis, emerging regulated cell death pathway induced by copper ions, has garnered attention recently. As cancer cells show altered metabolism comparatively higher needs, cuproptosis may play role in development ICC. However, studies investigating this possibility are currently lacking. Methods Single-cell bulk RNA sequence data were analyzed, correlations established between expression cuproptosis-related molecules ICC patient survival. Genes predicting survival used to create CUPT score using Cox LASSO regression tumor mutation burden (TMB) analysis. The CIBERSORT software was employed characterize immune infiltration within tumors. Furthermore, prediction, biological function enrichment, drug sensitivity analyses conducted explore potential implications signature. effects silencing solute carrier family 39 member 4 gene (SLC39A4) siRNA investigated assays measuring proliferation, colony formation, migration. Key genes detected western blotting. Results developed divided patients into high low groups. Those had significantly better prognosis longer In contrast, scores associated worse clinical outcomes TMB. Comparisons two groups also indicated differences infiltrate present Finally, we able identify 95 drugs potentially affecting pathway. Some these might be effective vitro experiments revealed that suppressing SLC39A4 lines resulted reduced It led increase upregulation key cuproptosis, namely ferredoxin 1 (FDX1) dihydrolipoyl transacetylase (DLAT). These findings strongly suggest cuproptosis-associated molecule pivotal metastasis Conclusions Changes signature can predict considerable accuracy. This supports notion influences diversity complexity microenvironment, mutational landscape, behavior Understanding hold promise for innovative strategies management disease.

Language: Английский

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