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Predicting CD27 expression and clinical prognosis in serous ovarian cancer using CT-based radiomics.Journal of Ovarian Research Jun 2024This study aimed to develop and evaluate radiomics models to predict CD27 expression and clinical prognosis before surgery in patients with serous ovarian cancer (SOC).
BACKGROUND
This study aimed to develop and evaluate radiomics models to predict CD27 expression and clinical prognosis before surgery in patients with serous ovarian cancer (SOC).
METHODS
We used transcriptome sequencing data and contrast-enhanced computed tomography images of patients with SOC from The Cancer Genome Atlas (n = 339) and The Cancer Imaging Archive (n = 57) and evaluated the clinical significance and prognostic value of CD27 expression. Radiomics features were selected to create a recursive feature elimination-logistic regression (RFE-LR) model and a least absolute shrinkage and selection operator logistic regression (LASSO-LR) model for CD27 expression prediction.
RESULTS
CD27 expression was upregulated in tumor samples, and a high expression level was determined to be an independent protective factor for survival. A set of three and six radiomics features were extracted to develop RFE-LR and LASSO-LR radiomics models, respectively. Both models demonstrated good calibration and clinical benefits, as determined by the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The LASSO-LR model performed better than the RFE-LR model, owing to the area under the curve (AUC) values of the ROC curves (0.829 vs. 0.736). Furthermore, the AUC value of the radiomics score that predicted the overall survival of patients with SOC diagnosed after 60 months was 0.788 using the LASSO-LR model.
CONCLUSION
The radiomics models we developed are promising noninvasive tools for predicting CD27 expression status and SOC prognosis. The LASSO-LR model is highly recommended for evaluating the preoperative risk stratification for SOCs in clinical applications.
Topics: Humans; Female; Ovarian Neoplasms; Prognosis; Tomography, X-Ray Computed; Middle Aged; Tumor Necrosis Factor Receptor Superfamily, Member 7; Cystadenocarcinoma, Serous; Aged; Adult; ROC Curve; Biomarkers, Tumor; Radiomics
PubMed: 38909269
DOI: 10.1186/s13048-024-01456-7 -
Nature Communications Jun 2024Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of...
Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here, we generate and characterize a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to aminopeptidase N (APN), the entry receptor for PDCoV. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.
Topics: Spike Glycoprotein, Coronavirus; Animals; Antibodies, Neutralizing; Swine; Antibodies, Viral; Epitopes; Humans; Deltacoronavirus; CD13 Antigens; Coronavirus Infections; Protein Domains; Protein Binding; Swine Diseases; HEK293 Cells
PubMed: 38909062
DOI: 10.1038/s41467-024-49693-0 -
Scientific Reports Jun 2024Non-small cell lung cancer (NSCLC)-originating cancer-associated fibroblasts (CAFs) expressing CD248 regulate interaction with immune cells to accelerate cancer...
Non-small cell lung cancer (NSCLC)-originating cancer-associated fibroblasts (CAFs) expressing CD248 regulate interaction with immune cells to accelerate cancer progression. Epithelial-mesenchymal transition (EMT) is a key feature of metastatic cells. In our pervious study, we found that CD248CAFs activated M2-polarized macrophages, enhancing the progression of NSCLC. However, it is yet unclear how CD248CAFs inducing M2-polarized macrophages induce EMT program in NSCLC cells. Herein, we examined CD248 expression from CAFs derived from NSCLC patient tumour tissues. Furthermore, we determined the influence of CD248 knock down CAFs on macrophages polarization. Next, we explored the influences of CD248-harboring CAFs-mediated M2 macrophage polarization to promote NSCLC cells EMT in vitro. We constructed fibroblasts specific CD248 gene knock out mice to examine the significance of CD248-harboring CAFs-induced M2-polarized macrophages to promote NSCLC cells EMT in vivo. Based on our analysis, CD248 is ubiquitously expressed within NSCLC-originating CAFs. CD248CAFs mediated macrophages polarized to M2 type macrophages. CD248CAFs induced M2 macrophage polarization to enhance NSCLC cells EMT both in vivo and in vitro. Our findings indicate that CD248-harboring CAFs promote NSCLC cells EMT by regulating M2-polarized macrophages.
Topics: Epithelial-Mesenchymal Transition; Carcinoma, Non-Small-Cell Lung; Cancer-Associated Fibroblasts; Humans; Animals; Lung Neoplasms; Macrophages; Mice; Antigens, CD; Mice, Knockout; Cell Line, Tumor; Antigens, Neoplasm
PubMed: 38906929
DOI: 10.1038/s41598-024-65435-0 -
Scientific Reports Jun 2024Our aim was to explore whether programmed death receptor-1 (PD-1) inhibitors would improve the prognosis of unresectable hepatocellular carcinoma (HCC) treated with...
Our aim was to explore whether programmed death receptor-1 (PD-1) inhibitors would improve the prognosis of unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus lenvatinib. In this single-center retrospective study, patients with unresectable HCC who underwent TACE and were administered lenvatinib with or without PD-1 inhibitors were enrolled and divided into the TACE + lenvatinib group and TACE + lenvatinib + PD-1 group. Overall survival (OS), progression-free survival (PFS) and tumor response were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1 and mRECIST). Treatment-related adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). In total, 35 eligible patients with unresectable HCC were included; 82.9% of patients had Hepatitis B virus (HBV) infection, and 88.6% of patients had liver cirrhosis. A total of 88.6% of patients had multiple tumors, and the median diameter of the largest tumor was 10.1 cm. A total of 14.3% of patients had extrahepatic metastasis, and 51.4% of patients had portal vein tumor thrombus. The percentages of BCLC stages A, B and C were 5.7%, 28.6% and 65.7%, respectively. There were 16 patients in the TACE + lenvatinib group and 19 patients in the TACE + lenvatinib + PD-1 group. The median follow-up time was 7.7 months (ranging from 1.7 to 31.6 months). Neither group reached the median overall survival. Under RECIST v1.1 criteria, the median PFS was 10.4 and 7.9 months in the TACE + lenvatinib and TACE + lenvatinib + PD-1 groups (HR, 1.13; 95% CI 0.45-2.84; p = 0.80), the objective response rates (ORR) were 31.3% and 31.6% (p > 0.05), and the disease control rates (DCR) were 93.8% and 78.9% (p > 0.05), respectively. Under mRECIST criteria, the median PFS was 10.4 and 10.1 months (HR, 0.98; 95% CI 0.38-2.54, p = 0.97), the ORR was 62.5% and 63.2% (p > 0.05), and the DCR was 93.8% and 73.7% (p > 0.05), respectively. Overall, AEs were relatively similar between the two groups. PD-1 inhibitors did not improve the PFS and tumor response of unresectable HCC treated with TACE plus lenvatinib. Hepatitis B infection, liver cirrhosis, portal vein tumor thrombus, multiple tumors and large tumor diameter may be potential factors that affect the efficacy of PD-1 inhibitors but need further validation.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Quinolines; Male; Female; Phenylurea Compounds; Retrospective Studies; Chemoembolization, Therapeutic; Middle Aged; Aged; Prognosis; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Adult
PubMed: 38906915
DOI: 10.1038/s41598-024-63571-1 -
International Journal of Biological... 2024Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and is highly...
Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and is highly expressed in proximal tubular epithelial cells (PTECs). Research shows that AOAH plays a critical role in infections and chronic inflammatory diseases, although its role in kidney injury is unknown. Here, we found that AOAH deletion led to exacerbated kidney injury and fibrosis after folic acid (FA) administration, which was reversed by overexpression of in kidneys. ScRNA-seq revealed that mice exhibited increased subpopulation of CD74 PTECs, though the percentage of total PTECs were decreased compared to WT mice after FA treatment. Additionally, exacerbated kidney injury and fibrosis seen in mice was attenuated via administration of methyl ester of (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), an inhibitor of macrophage inhibition factor (MIF) and CD74 binding. Finally, AOAH expression was found positively correlated with estimated glomerular filtration rate while negatively correlated with the degree of renal fibrosis in kidneys of CKD patients. Thus, our work indicates that AOAH protects against kidney injury and fibrosis by inhibiting renal tubular epithelial cells CD74 signaling pathways. Targeting kidney AOAH represents a promising strategy to prevent renal fibrosis progression.
Topics: Animals; Mice; Macrophages; Carboxylic Ester Hydrolases; Humans; Antigens, Differentiation, B-Lymphocyte; Renal Insufficiency, Chronic; Mice, Inbred C57BL; Male; Histocompatibility Antigens Class II; Folic Acid; Kidney Tubules; Fibrosis; Mice, Knockout; Epithelial Cells
PubMed: 38904010
DOI: 10.7150/ijbs.91237 -
Frontiers in Immunology 2024Antigen-driven human effector-memory CD8+ T cells expressing low levels of the CD8β chain have been previously described. However, little is known on a possible...
Antigen-driven human effector-memory CD8+ T cells expressing low levels of the CD8β chain have been previously described. However, little is known on a possible antigen-independent trigger. We have examined the impact that IL-15 has on the expression of CD8β on purified human naïve CD8+ T cells after CFSE labeling and culture with IL-15. As expected, IL-15 induced naïve CD8+ T cells to proliferate and differentiate. Remarkably, the process was associated with a cell-cycle dependent down-modulation of CD8β from the cell surface, leading to the generation of CD8αβ and CD8αβ (i.e., CD8αα) T cells. In contrast, expression of the CD8α chain remained steady or even increased. Neither IL-2 nor IL-7 reproduced the effect of IL-15. Determination of mRNA levels for CD8α and CD8β isoforms by qPCR revealed that IL-15 promoted a significant decrease in mRNA levels of the CD8β M-4 isoform, while levels of the M-1/M-2 isoforms and of CD8α increased. Noteworthy, CD8+ T cell blasts obtained after culture of CD8+ T cells with IL-15 showed a cell-cycle dependent increase in the level of the tyrosine kinase Lck, when compared to CD8+ T cells at day 0. This study has shown for the first time that IL-15 generates CD8αααβ and CD8αααβ T cells containing high levels of Lck, suggesting that they may be endowed with unique functional features.
Topics: Humans; Interleukin-15; CD8-Positive T-Lymphocytes; CD8 Antigens; Lymphocyte Activation; Cells, Cultured; Cell Differentiation; Cell Proliferation; Down-Regulation
PubMed: 38903513
DOI: 10.3389/fimmu.2024.1252439 -
Frontiers in Immunology 2024The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based... (Review)
Review
The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade.
Topics: Humans; Immune Checkpoint Inhibitors; Drug Resistance, Neoplasm; Tumor Microenvironment; Neoplasms; Animals; Immunotherapy; B7-H1 Antigen; Programmed Cell Death 1 Receptor
PubMed: 38903504
DOI: 10.3389/fimmu.2024.1384121 -
Frontiers in Immunology 2024Macrophages play essential roles in maintaining tissue homeostasis and immune defence. However, their extensive infiltration into tumours has been linked to adverse...
Macrophages play essential roles in maintaining tissue homeostasis and immune defence. However, their extensive infiltration into tumours has been linked to adverse outcomes in multiple human cancers. Within the tumour microenvironment (TME), tumour-associated macrophages (TAMs) promote tumour growth and metastasis, making them prime targets for cancer immunotherapy. Recent single-cell analysis suggest that proliferating TAMs accumulate in human cancers, yet their origins and differentiation pathways remain uncertain. Here, we show that a subpopulation of CD163+ TAMs proliferates within the TME of melanoma, lung cancer, and breast cancer. Consistent with their potential role in suppressing anti-tumour activities of T cells, CD163+ TAMs express a range of potent immunosuppressive molecules, including PD-L1, PD-L2, IL-10, and TGF-β. Other phenotypic markers strongly suggested that these cells originate from CD14+ CCR2+ monocytes, a cell population believed to have minimal capacity for proliferation. However, we demonstrate that certain myelopoietic cytokines commonly available within the TME induce robust proliferation of human monocytes, especially the combination of interleukin 3 (IL-3) and Macrophage Colony-Stimulating Factor 1 (M-CSF). Monocytic cells cultured with these cytokines efficiently modulate T cell proliferation, and their molecular phenotype recapitulates that of CD163+ TAMs. IL-3-driven proliferation of monocytic cells can be completely blocked by IL-4, associated with the induction of CDKN1A, alongside the upregulation of transcription factors linked to dendritic cell function, such as BATF3 and IRF4. Taken together, our work suggests several novel therapeutic routes to reducing immunosuppressive TAMs in human tumours, from blocking chemokine-mediated recruitment of monocytes to blocking their proliferation.
Topics: Humans; Monocytes; Cell Proliferation; Tumor Microenvironment; Tumor-Associated Macrophages; Neoplasms; Antigens, CD; Female; Macrophages; Receptors, Cell Surface; Antigens, Differentiation, Myelomonocytic; Cytokines; T-Lymphocytes; Breast Neoplasms
PubMed: 38903497
DOI: 10.3389/fimmu.2024.1412076 -
Stem Cell Research & Therapy Jun 2024Human hematopoietic stem cell (HSC)-transferred humanized mice are valuable models for exploring human hematology and immunology. However, sufficient recapitulation of...
Human hematopoietic stem cell (HSC)-transferred humanized mice are valuable models for exploring human hematology and immunology. However, sufficient recapitulation of human hematopoiesis in mice requires large quantities of enriched human CD34 HSCs and total-body irradiation for adequate engraftment. Recently, we generated a NOG mouse strain with a point mutation in the c-kit tyrosine kinase domain (W41 mutant; NOGW mice). In this study, we examined the ability of NOGW mice to reconstitute human hematopoietic cells. Irradiated NOGW mice exhibited high engraftment levels of human CD45 cells in the peripheral blood, even when only 5,000-10,000 CD34 HSCs were transferred. Efficient engraftment of human CD45 cells was also observed in non-irradiated NOGW mice transferred with 20,000-40,000 HSCs. The bone marrow (BM) of NOGW mice exhibited significantly more engrafted human HSCs or progenitor cells (CD34CD38 or CD34CD38 cells) than the BM of NOG mice. Furthermore, we generated a human cytokine (interleukin-3 and granulocyte-macrophage colony-stimulating factor) transgenic NOG-W41 (NOGW-EXL) mouse to achieve multilineage reconstitution with sufficient engraftment of human hematopoietic cells. Non-irradiated NOGW-EXL mice showed significantly higher engraftment levels of human CD45 and myeloid lineage cells, particularly granulocytes and platelets/megakaryocytes, than non-irradiated NOGW or irradiated NOG-EXL mice after human CD34 cell transplantation. Serial BM transplantation experiments revealed that NOGW mice exhibited the highest potential for long-term HSC compared with other strains. Consequently, c-kit mutant NOGW-EXL humanized mice represent an advanced model for HSC-transferred humanized mice and hold promise for widespread applications owing to their high versatility.
Topics: Animals; Humans; Proto-Oncogene Proteins c-kit; Hematopoiesis; Mice; Hematopoietic Stem Cells; Hematopoietic Stem Cell Transplantation; Mice, Transgenic; Cell Lineage; Antigens, CD34; Interleukin-3; Mutation
PubMed: 38902833
DOI: 10.1186/s13287-024-03799-w -
Scientific Reports Jun 2024Acute myeloid leukaemia (AML) is an aggressive leukaemia characterised by uncontrolled blast cell proliferation. miRNAs and Clusters of Differentiation (CD) molecules...
Acute myeloid leukaemia (AML) is an aggressive leukaemia characterised by uncontrolled blast cell proliferation. miRNAs and Clusters of Differentiation (CD) molecules play essential roles in AML progression. This study aims to investigate the effect of COVID-19 on the expression of circulating miRNA and CD molecules in AML. This cross-sectional study recruited 32 AML patients and 20 controls. Blood samples were collected and analysed using molecular cytogenetic, miRNA/mRNA expression, and flow cytometry techniques. The expression of miRNAs varied significantly between patients with AML and control individuals. The co-expression of these miRNAs was higher (P < 0.05), indicating that the presence of one miRNA led to increased expression of other miRNAs. A differential correlation was observed between miRNAs and CD markers. Additionally, miRNA 16, miRNA 21, and miRNA 221 showed significant downregulation (P < 0.05 and P < 0.01, respectively) in AML patients with COVID-19 infection compared to those without a disease. Interestingly, this study identified a higher expression level (P < 0.01) of miRNA 137 as a novel biomarker for AML patients. Moreover, the expression of miRNA 137 showed a high correlation (P < 0.05) with most of the CD markers examined in this study and FISH features data. Furthermore, a strong correlation (P < 0.01) was observed between CD markers and miRNA among AML patients with positive and negative COVID-19 infection. These data demonstrated that COVID-19 contributed to increased expression of microRNAs in AML patients. MicroRNA 137 was identified as a novel microRNA that exhibited significant differences between patients and healthy individuals, highlighting its role in AML pathogenesis.
Topics: Humans; Leukemia, Myeloid, Acute; COVID-19; Male; Female; MicroRNAs; Middle Aged; Adult; Cross-Sectional Studies; Aged; Biomarkers, Tumor; SARS-CoV-2; Antigens, CD
PubMed: 38902412
DOI: 10.1038/s41598-024-64775-1