cxcl13 protein levels  (Human Protein Atlas)

Journal: Nature

Article Title: ACLY inhibition promotes tumour immunity and suppresses liver cancer

doi: 10.1038/s41586-025-09297-0

Figure Lengend Snippet: a , Volcano plot of bulk RNA-seq of tumours showing upregulated and downregulated genes at early or late timepoints from Acly- KO ( n = 12) versus WT ( n = 9) mice. Significance was determined by Wald test with a false discovery-adjusted threshold of 5% as implemented in DESeq2. Horizontal dashed lines demarcate the P value threshold at a 5% false discovery rate (FDR). b , Gene Ontology analysis of selected biological processes involving significantly upregulated genes in tumours from Acly -KO ( n = 12) versus WT ( n = 9) mice. FC, fold change. c , Top 10 Gene Ontology biological processes (GOBP) from clusters identified among significantly upregulated gene sets in tumours from Acly -KO ( n = 12) versus WT ( n = 9) mice. NES, normalized enrichment score. d , Correlation between B cell populations and Acly expression in tumours from WT ( n = 9) and Acly -KO ( n = 12) mice. Confidence bands denote the upper and lower bounds of the 95% confidence interval. Significance of association was determined by a two-sided Student’s t -test of regression coefficients and at a false discovery-adjusted threshold of 5%. e – p , Spatial transcriptomic analysis of livers from WT and Acly -KO mice and vehicle or EVT0185-treated mice. Cluster analysis representing the number of cell types in the liver and tumour ( e , k ). Umapharmony integration analysis showing increased B cells in Acly- KO ( f ) and in EVT0185-treated ( l ) mice. The top upregulated pathways in HCC cells from Acly -KO ( g ) and EVT0185-treated ( m ) mice. Statistical analysis was performed using Fisher’s exact test. Expression level of metabolic genes ( h , n ). Expression of markers of subtypes of B cells ( i , o ). The box-and-whisker plots are defined by the median with the first quartile (Q1), third quartile (Q3), minimum (Q1 − 1.5 × interquartile range (IQR)) and maximum (Q3 + 1.5 × IQR). Cxcl13 expression levels in HCC cells ( j , p ). GC, germinal centre; HSC, hepatic stellate cell; MZ, marginal zone; Tr, regulatory; VSMC, vascular smooth muscle cell.

Article Snippet: Liver tumour CXCL13 protein levels were determined using the mouse CXCL13/BLC/BCA-1 Quantikine ELISA Kit (MCX130, R&D Systems) following the manufacturer’s instructions.

Techniques: RNA Sequencing, Expressing, Whisker Assay

Journal: Nature

Article Title: ACLY inhibition promotes tumour immunity and suppresses liver cancer

doi: 10.1038/s41586-025-09297-0

Figure Lengend Snippet: a-b , Immune cell markers expressed in different cell types in a , WT and Acly KO and b , Vehicle and EVT0185-treated mice. c , Top upregulated pathways in B cells in Acly KO or EVT0185-treated mice (spatial transcriptomics analysis). Statistical analysis was performed using Fisher’s Exact test. d and e , Single seq analysis of d , WD-DEN and e , WD-CCl 4 mouse livers showing top upregulated pathways in B cells. Statistical analysis was performed using a one-sided hypergeometric test (enrichGO); p-values adjusted by Benjamini-Hochberg. f , Cxcl13 mRNA expression analyzed from publicly available RNA-seq dataset in WT and Acly KO DEN tumors cultured in vitro ( GSE223966 ) . Boxplot lines represent the first quartile, median, and third quartile. Whiskers connect the minimum and maximum values. Significance was ascertained by an unpaired two-tailed t-test between Acly KO vs WT (n = 4 hepatocellular carcinoma cell lines derived from DEN-induced tumors in Acly f/f mice).

Article Snippet: Liver tumour CXCL13 protein levels were determined using the mouse CXCL13/BLC/BCA-1 Quantikine ELISA Kit (MCX130, R&D Systems) following the manufacturer’s instructions.

Techniques: Expressing, RNA Sequencing, Cell Culture, In Vitro, Two Tailed Test, Derivative Assay

Journal: Nature

Article Title: ACLY inhibition promotes tumour immunity and suppresses liver cancer

doi: 10.1038/s41586-025-09297-0

Figure Lengend Snippet: a and b , Quantification of lipid droplet area was extrapolated by converting the PLIN-2 signal into a mask and quantifying the area covered by this mask per 400 × 400 micron field of view (FOV). These calculations were performed in ImageJ using custom scripts. Each dot represents a single FOV, Wilcoxon non-parametric unpaired two-sided test. Acly KO (n = 188) vs WT (n = 170) FOVs from n = 4 mice/group. c , CXCL13 protein level in tumors from WT and Acly KO mice; mean ± SEM, n = 5 mice/group; unpaired two-tailed t-test. d , Representative images showing B cells at tumor centre and periphery (Orange star: Tumor front (border-periphery), Black star: Surrounding non-tumoral hepatic tissue). e , B cell aggregations in Acly KO tumor (Orange star: Tumor, Black star: Non-tumoral liver tissue, Blue star: B Cell aggregations). f , Heatmap of cell neighborhoods hierarchically sorted by cell phenotype and showing relative cell abundances. ( g-j, l-n ) WD-DEN mice treated with Vehicle or EVT0185. g , Representative MIBI images of liver tumors. h , B cell, and i , T cell counts from regions representing the tumor lesion interface with the liver; mean ± SEM, n = 4 mice/group; unpaired Wilcoxon non-parametric unpaired two-sided test. j , CD19+ positive cells count/mm 2 tumor area; mean ± SEM, Vehicle (n = 29) and EVT0185 (n = 21) lesions; unpaired two-tailed t-test. k , CD3+ positive cells count/mm 2 tumor area; mean ± SEM, WT (n = 12) and Acly KO (n = 10) lesions; unpaired two-tailed t-test. l , CD3+ positive cells count/mm 2 tumor area; mean ± SEM, Vehicle (n = 29) and EVT0185 (n = 21) lesions; unpaired two-tailed t-test. m , Percentage of mice with/without B cells in TLS. n , TLS in EVT-treated mouse compared with vehicle control. o , GO enrichment analysis showing upregulated pathways related to complement activation in B cells in the EVT0185-treated group relative to Vehicle. Statistical analysis was performed using one-sided hypergeometric test (enrichGO); p-values adjusted by Benjamini-Hochberg.

Article Snippet: Liver tumour CXCL13 protein levels were determined using the mouse CXCL13/BLC/BCA-1 Quantikine ELISA Kit (MCX130, R&D Systems) following the manufacturer’s instructions.

Techniques: Two Tailed Test, Control, Activation Assay

Journal: Nature

Article Title: ACLY inhibition promotes tumour immunity and suppresses liver cancer

doi: 10.1038/s41586-025-09297-0

Figure Lengend Snippet: a , Differential expression analysis comparing MASH-HCC (n = 53) and non-tumor adjacent liver (n = 29), MASH liver (n = 74), cirrhotic liver (n = 8), and healthy liver tissue (n = 6); two-tailed t-test; 5% FDR as implemented in limma. b , Overlap between significantly upregulated and downregulated genes in each pairwise comparison. c , Gene expression of lipogenic enzymes acetyl-CoA carboxylase ( ACACA or ACACB ), ACSS2 , and FASN across disease states (MASH-HCC, n = 53; non-tumor adjacent, n = 29; MASH liver, n = 74; cirrhotic liver, n = 8; healthy liver, n = 6). Boxplot lines represent the first quartile, median, and third quartile. Whiskers connect the minimum and maximum values. d , ACLY upregulation in human MASH-HCC compared to all other tissue types using scRNAseq samples. Significance assessed using Wilcoxon rank-sum tests comparing each condition to MASH-HCC, with p-values adjusted using the Benjamini-Hochberg method. Exact p-adj values: vs healthy P adj = 6.9 × 10 −247 , vs MALSD P adj = 1.0 × 10 −16 , vs non-tumor adjacent P adj = 1.6 × 10 −18 . e , Differential expression analysis of genes associated with ACLY expression in MASH-HCC; two-tailed t-test; 5% FDR as implemented in limma. f , Principal component embeddings of genes differentially expressed with respect to ACLY expression validate stratification of MASH-HCC tissues by high, medium, and low ACLY expression levels. g , Upregulation of CXCL13 among human MASH-HCC samples with reduced (bottom tertile, n = 18) relative to elevated (top tertile, n = 18) ACLY expression. Significance determined by two-tailed t-test with a false discovery adjusted threshold of 5% as implemented in limma. Boxplot lines represent the first quartile, median, and third quartile. Whiskers connect the minimum and maximum values. h , Identification of co-expression modules associated with ACLY expression and immune features. i , Significant biological processes associated with the immune and ACLY associated gene co-expression module.

Article Snippet: Liver tumour CXCL13 protein levels were determined using the mouse CXCL13/BLC/BCA-1 Quantikine ELISA Kit (MCX130, R&D Systems) following the manufacturer’s instructions.

Techniques: Quantitative Proteomics, Two Tailed Test, Comparison, Gene Expression, Expressing

Journal: Medicine

Article Title: Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

doi: 10.1097/MD.0000000000040272

Figure Lengend Snippet: (A) Protein–protein intersection (PPI) network of differentially expressed genes (DEGs); (B) twenty core genes in the PPI network; (C) prognostic DEGs; (D) core genes CXCL13 and CD3E on the Venn diagram; (E) meta-analysis for OS based on expression levels of CXCL13 in OC patients.

Article Snippet: The Human Protein Atlas (HPA) ( http://proteinatlas.org ) [ ] was used to analyze CXCL13 protein levels.

Techniques: Expressing

Journal: Medicine

Article Title: Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

doi: 10.1097/MD.0000000000040272

Figure Lengend Snippet: TCGA and GETx datasets show expression of CXCL13 is statistical different between OC and normal tissue (A) and in different pathological stages of OC (B). (C) Oncomine database verifies the expression of CXCL13 ; (D) the negative staining of CXCL13 in 2 normal tissues; (E) the negative (0), low (1), and medium (2) immunohistochemical staining of CXCL13 in 3 OC patients.

Article Snippet: The Human Protein Atlas (HPA) ( http://proteinatlas.org ) [ ] was used to analyze CXCL13 protein levels.

Techniques: Expressing, Negative Staining, Immunohistochemical staining, Staining

Journal: Medicine

Article Title: Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

doi: 10.1097/MD.0000000000040272

Figure Lengend Snippet: Survival curves of OC patients in CXCL13 high- and low-expression groups.

Article Snippet: The Human Protein Atlas (HPA) ( http://proteinatlas.org ) [ ] was used to analyze CXCL13 protein levels.

Techniques: Expressing

Journal: Medicine

Article Title: Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

doi: 10.1097/MD.0000000000040272

Figure Lengend Snippet: Gene set enrichment analysis enrichment pathway of CXCL13 expression profile in OC patients.

Article Snippet: The Human Protein Atlas (HPA) ( http://proteinatlas.org ) [ ] was used to analyze CXCL13 protein levels.

Techniques: Expressing

Journal: Medicine

Article Title: Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

doi: 10.1097/MD.0000000000040272

Figure Lengend Snippet: Correlation between the expression of CXCL13 and infiltration of various immune cell components in the tumor microenvironment. (A) CD8 + T cell; (B) activated CD4 + memory T cell; (C) memory B cell; (D) M1 macrophage cell; (E) follicular helper T cell; (F) resting CD4 + memory T cell; (G) naive B cell; (H) M2 macrophage cell; (I) activated myeloid dendritic cell; (J) neutrophils.

Article Snippet: The Human Protein Atlas (HPA) ( http://proteinatlas.org ) [ ] was used to analyze CXCL13 protein levels.

Techniques: Expressing

Journal: Medicine

Article Title: Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

doi: 10.1097/MD.0000000000040272

Figure Lengend Snippet: (A) Correlation between the expression of CXCL13 and PD-1 of TCGA-OC samples; (B) correlation between the expression of CXCL13 and CR/PR, SD/PD in mUC samples after receiving PD-L1 blocking therapy (CR = complete response, PR = partial response, PD = progressive disease, SD = stable disease). Survival curves of mUC patients with high- and low- CXCL13 expression in SD/PD (C) and CR/PR (D) group.

Article Snippet: The Human Protein Atlas (HPA) ( http://proteinatlas.org ) [ ] was used to analyze CXCL13 protein levels.

Techniques: Expressing, Blocking Assay

Journal: Molecular Therapy Oncolytics

Article Title: CXCR5 guides migration and tumor eradication of anti-EGFR chimeric antigen receptor T cells

doi: 10.1016/j.omto.2021.07.003

Figure Lengend Snippet: Restricted normal T cell expression of CXCR5 and upregulation of CXCL13 in non-small cell lung cancer (NSCLC) (A) The expression of CXCL13 in patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) using the online tool of GEPIA. (B) CXCL13 protein expressions in NSCLC tissues were confirmed by immunohistochemistry on two tissue microarray slides (NSC157 and LC20813b). The intensity of immunostaining was graded as follows: −, negative; +, weak; ++, moderate; or +++, strong. (C) Expression of CXCL13 by immunohistochemistry. The subpanels show negative expression of CXCL13 (−), weak (+), moderate (++), and strong (+++) expressions of CXCL13 in tumor tissues ( ×400). (D) ELISA quantification of the level of CXCL13 protein in plasma samples (healthy donors n = 34, NSCLC patient donors n = 95). Single dot represents individual plasma sample. Error bars represent mean ± SD. ∗∗∗p < 0.001. (E) FACS analysis of the expression of different chemokine receptors from resting and activated T cells. Single dot represents individual sample. Error bars represent mean ± SD for each T cell population (n = 12).

Article Snippet: The CXCL13 level in the blood plasma was quantified by the CXCL13 ELISA kit from OriGene (catalog number [cat. no.] EA800062) according to the manufacturer’s instructions.

Techniques: Expressing, Immunohistochemistry, Microarray, Immunostaining, Enzyme-linked Immunosorbent Assay

Journal: Molecular Therapy Oncolytics

Article Title: CXCR5 guides migration and tumor eradication of anti-EGFR chimeric antigen receptor T cells

doi: 10.1016/j.omto.2021.07.003

Figure Lengend Snippet: Evaluation of the antitumor efficacy and chemotaxis migration of EGFR-CXCR5-CAR-T cells in vitro (A) Analysis of the cytotoxicity of EGFR-CXCR5-CAR-T cells against PC9, A549, and K562 cells. Tumor cell killing was measured via an IncuCyte assay over 48 h. SYTOX Green and CellTrace Far Red double-positive tumor cells (yellow) were calculated. Error bars represent mean ± SD for each time point. (B) Real-time cell killing image. Target cells were red, and CAR-T cells were green. (C) Cytokine production by CAR-T cells co-cultured with PC9 tumor cells. CAR-T cells were co-cultured 10:1 with tumor cells in 96-well plates for 20 h. Levels of IFN-γ and IL-2 in supernatant were determined by ELISA. Error bars represent mean ± SD for each group. (D) Chemotaxis migration of CAR-Ts toward various concentrations of recombinant human CXCL13 at different time courses of 4 h, 8 h, and 16 h. Error bars represent mean ± SD for each group (n = 3). ∗p < 0.05 derived via unpaired t test. (E) CAR-T cell proliferation assay with indicated CAR-T cells cocultured with various concentrations of recombinant human CXCL13.

Article Snippet: The CXCL13 level in the blood plasma was quantified by the CXCL13 ELISA kit from OriGene (catalog number [cat. no.] EA800062) according to the manufacturer’s instructions.

Techniques: Chemotaxis Assay, Migration, In Vitro, Cell Culture, Enzyme-linked Immunosorbent Assay, Recombinant, Derivative Assay, Proliferation Assay

Journal: Molecular Therapy Oncolytics

Article Title: CXCR5 guides migration and tumor eradication of anti-EGFR chimeric antigen receptor T cells

doi: 10.1016/j.omto.2021.07.003

Figure Lengend Snippet: In vivo tracking of the migration of 89 Zr-oxine-labeled CAR-T to A549 and A549-CXCL13 tumors using micro-PET/CT scan (A) EGFR expression in the A549 cell line stably expressing the CXCL13 gene (A549-CXCL13) after lentiviral transduction and selection. (B) Increased secretion of CXCL13 generated by A549-CXCL13 cells. ∗∗∗p < 0.001. (C) The effects of 89 Zr-oxine labeling on T cell proliferation. (D) Whole-body PET imaging, quantitative PET analysis, and biodistribution of 89 Zr-labeled T cells in tumor-bearing mice. 89 Zr-labeled mock T cells, 89 Zr-EGFR-CAR-T cells, or 89 Zr-EGFR-CXCR5-CAR-T cells were tail-vein injected into NSG mice inoculated with A549 tumor cells at the left and A549-CXCL13 tumor cells at the right side. Isotopic distribution of 89 Zr was quantified and plotted in a coronal horizon map at different time points of 2, 24, 72, and 168 h post-injection. The red and green circles represent the A549 tumor region and A549-CXCL13 tumor region, respectively. (E) Accumulated isotope signaling in A549 tumor region (green circle) and A549-CXCL13 tumor region (red circle). The percentage injection dose rate ([%ID]/g value) was calculated. Error bars represent mean ± SD for each group (n = 3).

Article Snippet: The CXCL13 level in the blood plasma was quantified by the CXCL13 ELISA kit from OriGene (catalog number [cat. no.] EA800062) according to the manufacturer’s instructions.

Techniques: In Vivo, Migration, Labeling, Micro-PET, Computed Tomography, Expressing, Stable Transfection, Transduction, Selection, Generated, Imaging, Injection

Journal: Molecular Therapy Oncolytics

Article Title: CXCR5 guides migration and tumor eradication of anti-EGFR chimeric antigen receptor T cells

doi: 10.1016/j.omto.2021.07.003

Figure Lengend Snippet: Antitumor efficacy of CAR-T cells in vivo (A) Serial bioluminescence imaging of NSG mice injected subcutaneously with A549 luc cells on the left flank and A549 luc -CXCL13 cells on the right flank. 10 days after tumor engraftment, the mice were injected with 5 × 10 5 CAR + T cells as indicated. n = 5 mice per group. Error bars represent mean ± SD for each time point (n = 5). (B) The tumor volume of the left tumors (A549 luc ) and right tumors (A549 luc -CXCL13) over 28 days was measured. Error bars represent mean ± SD for each time point (n = 5). (C) The copy number of CAR gene in the left and right tumor tissues was analyzed. ∗∗p < 0.01.

Article Snippet: The CXCL13 level in the blood plasma was quantified by the CXCL13 ELISA kit from OriGene (catalog number [cat. no.] EA800062) according to the manufacturer’s instructions.

Techniques: In Vivo, Imaging, Injection

Journal: Molecular Therapy Oncolytics

Article Title: CXCR5 guides migration and tumor eradication of anti-EGFR chimeric antigen receptor T cells

doi: 10.1016/j.omto.2021.07.003

Figure Lengend Snippet: Addition of CXCR5 facilitates T cell migration The chemokine CXCL13 is highly expressed in various tumors including lung carcinoma, whereas the classical CAR-T does not effectively infiltrate into tumor regions due to the absence of CXCR5 receptor expression. Chemotactic movement is a taxis in response to a chemical concentration gradient. When CAR-T cells are modified with the CXCR5 receptor, the motorized CAR-T cells could infiltrate into the tumor site along the gradient of CXCL13 to further clear the tumor cells.

Article Snippet: The CXCL13 level in the blood plasma was quantified by the CXCL13 ELISA kit from OriGene (catalog number [cat. no.] EA800062) according to the manufacturer’s instructions.

Techniques: Migration, Expressing, Concentration Assay, Modification