Purpose: At present, dysfunctional CD8 T-cells in the nasopharyngeal carcinoma (NPC) tumor immune microenvironment (TIME) have caused unsatisfactory immunotherapeutic effects, such as a low response rate of anti-PD-L1 therapy. Therefore, there is an urgent need to identify reliable markers capable of accurately predicting immunotherapy efficacy.
Methods: Utilizing various algorithms for immune-infiltration evaluation, we explored the role of EIF3C in the TIME. We next found the influence of EIF3C expression on NPC based on functional analyses and RNA sequencing. By performing correlation and univariate Cox analyses of CD8 Tcell markers from scRNA-seq data, we identified four signatures, which were then used in conjunction with the lasso algorithm to determine corresponding coefficients in the resulting EIF3C-related CD8 T-cell signature (ETS). We subsequently evaluated the prognostic value of ETS using univariate and multivariate Cox regression analyses, Kaplan-Meier curves, and the area under the receiver operating characteristic curve (AUROC).
Results: Our results demonstrate a significant relationship between low expression of EIF3C and high levels of CD8 T-cell infiltration in the TIME, as well as a correlation between EIF3C expression and progression of NPC. Based on the expression levels of four EIF3C-related CD8 T-cell marker genes, we constructed the ETS predictive model for NPC prognosis, which demonstrated success in validation. Notably, our model can also serve as an accurate indicator for detecting immunotherapy response.
Conclusion: Our findings suggest that EIF3C plays a significant role in NPC progression and immune modulation, particularly in CD8 T-cell infiltration. Furthermore, the ETS model holds promise as both a prognostic predictor for NPC patients and a tool for adjusting individualized immunotherapy strategies.
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http://dx.doi.org/10.1007/s00432-023-05552-x | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
ADAR is highly expressed and correlated with poor prognosis in hepatocellular carcinoma (HCC), yet the role of its constitutive isoform ADARp110 in tumorigenesis remains elusive. We investigated the role of ADARp110 in HCC and underlying mechanisms using clinical samples, a hepatocyte-specific knock-in mouse model, and engineered cell lines. ADARp110 is overexpressed and associated with poor survival in both human and mouse HCC.
View Article and Find Full Text PDFImmun Inflamm Dis
January 2025
Department of Medical and Surgical Sciences & Neurosciences, Respiratory Diseases Unit, Siena University Hospital, Siena, Tuscany, Italy.
Background: Post-coronavirus disease 19 lung fibrosis (PCLF) shares common immunological abnormalities with idiopathic pulmonary fibrosis (IPF), characterized by an unbalanced cytokine profile being associated with the development of lung fibrosis. The aim of the present study was to analyze and compare the different subsets of CD4- and CD8-T cells, along with specific cytokine expression patterns, in peripheral blood (PB) from patients affected by PCLF and IPF and healthy controls (HCs).
Methods: One-hundred patients followed at the Rare Lung Disease Center of Siena University Hospital were enrolled.
Mol Cancer
January 2025
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.
View Article and Find Full Text PDFNat Cancer
January 2025
State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Terminal exhaustion is a critical barrier to antitumor immunity. By integrating and analyzing single-cell RNA-sequencing and single-cell assay for transposase-accessible chromatin with sequencing data, we found that ETS variant 7 (ETV7) is indispensable for determining CD8 T cell fate in tumors. ETV7 introduction drives T cell differentiation from memory to terminal exhaustion, limiting antiviral and antitumor efficacy in male mice.
View Article and Find Full Text PDFNat Commun
January 2025
Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Immune functions decline with aging, leading to increased susceptibility to various diseases including tumors. Exploring aging-related molecular targets in elderly patients with cancer is thus highly sought after. Here we find that an ER transmembrane enzyme, sterol O-acyltransferase 2 (SOAT2), is overexpressed in regulatory T (Treg) cells from elderly patients with lung squamous cell carcinoma (LSCC), while radiomics analysis of LSCC patients associates increased SOAT2 expression with reduced immune infiltration and poor prognosis.
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