- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Drug Transport and Resistance Mechanisms
- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Tryptophan and brain disorders
- Inflammatory Biomarkers in Disease Prognosis
- Lung Cancer Diagnosis and Treatment
- Advanced Numerical Methods in Computational Mathematics
- Computational Fluid Dynamics and Aerodynamics
- Cancer, Hypoxia, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Treatments and Mutations
- Chemokine receptors and signaling
- Inertial Sensor and Navigation
- Cancer Research and Treatments
- Lung Cancer Research Studies
- Reservoir Engineering and Simulation Methods
- Distributed and Parallel Computing Systems
Taiwan Power (Taiwan)
2024
Fudan University
2023-2024
Zhongshan Hospital
2019-2024
Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells HCC, suggesting that a better understanding of intrinsic processes by which tumor regulate macrophages could help identify strategies to improve response immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members various functions, we investigated role specific SLAM receptors immunobiology HCC. Comparison transcriptomic landscapes...
Abstract Background The efficacy of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) is poor and great heterogeneity among individuals. Chemokines are highly correlated with tumor response. Here, we aimed to identify an effective chemokine for predicting the immunotherapy HCC. Methods Chemokine C‐C motif ligand 21 (CCL21) was screened by transcriptomic analysis tissues from HCC patients different responses ICIs. least absolute shrinkage selection operator (LASSO)...
<div>Abstract<p>Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells HCC, suggesting that a better understanding of intrinsic processes by which tumor regulate macrophages could help identify strategies to improve response immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members various functions, we investigated role specific SLAM receptors immunobiology HCC. Comparison...
<p>(A) Top: Schematic showing the administration schedule of clophosome in indicated orthotopic HCC mouse models. Bottom: Gross appearance liver bearing Hepa1-6 tumors treatment groups. (B) The tumor weight and volume each group at study endpoint (5 mice per group). NS, not significant, **P<0.01, ***P<0.001, one-way ANOVA with a post hoc LSD test.</p>
<p>(A) Representative IHC staining images showing the expressions of SLAMF7, p-STAT1, and p-STAT3 in HCC samples from Fudan LCI cohort. Scale bar: 200 μm (left) 20 (right). (B) immunofluorescence infiltration levels (right) exhausted T cells (CD8+ PD-1+ TCF1-) tumors with high low SLAMF7 protein expression 20μm. *P<0.05, Student’s t test.</p>
<p>(A) Representative IHC staining images showing the expressions of SLAMF7 and CCL2 in HCC samples. Scale bar: 200 μm (left) 20 (right). (B) The prognostic prediction performances combination with for OS DFS our Fudan LCI cohort.</p>
<p>(A-B) qPCR and ELISA analyses of CCL2 transcriptional secretory levels in the indicated HCC cells. (C-D) Flow cytometry analysis CD80 CD206 expressions THP-1-differentiated macrophages cocultured with cells presence recombinant protein or neutralizing antibody. (E-F) Chemotaxis assays showing effect signaling on SLAMF7-regulated migration using treatments. (G) Left: Gross appearance liver bearing orthotopic tumors treatment groups. Right: The tumor weight volume each group (5 mice...
<p>(A) Top: Schematic showing the administration schedule of clophosome in indicated orthotopic HCC mouse models. Bottom: Gross appearance liver bearing Hepa1-6 tumors treatment groups. (B) The tumor weight and volume each group at study endpoint (5 mice per group). NS, not significant, **P<0.01, ***P<0.001, one-way ANOVA with a post hoc LSD test.</p>
<p>(A-B) Flow cytometry assays of tumor infiltration proportions CD11b+ F4/80+ MHC-II+ macrophages and CD3+ CD8+ PD-1+ T cells in orthotopic Hepa1-6 tumors with Slamf7 overexpression control groups. (C) Heatmap showing the immunological activity ssGSEA scores samples from TCGA-LIHC cohort. The upper horizontal bars represent expression level SLAMF7. (D) Correlation matrix relationships between SLAMF7 various immune (E) Violin diagrams percentages 22 cell types calculated using...
<p>(A) Immunoblot assay of SHB protein level in the indicated HCC cells. (B-C) assays phosphorylated and non-phosphorylated SHIP1, K63-linked ubiquitinated TRAF6 cells with without silence.</p>
<p>(A) Representative IHC staining images showing the expressions of SLAMF7 and CCL2 in HCC samples. Scale bar: 200 μm (left) 20 (right). (B) The prognostic prediction performances combination with for OS DFS our Fudan LCI cohort.</p>
<p>(A) Flow cytometry analyses of CD80 and CD206 expressions in THP-1-differentiated macrophages cocultured with the indicated HCC cells. (B) MHC-II BMDMs (C) qPCR M1 M2 marker genes transcription levels (D-E) Chemotaxis assays showing effect supernatants from coculture systems on migration ability BMDMs. Scale bar: 100 μm. (F) The correlations intra-tumoral SLAMF7 expression CXCL10, CXCL9, ARG1 TCGA-LIHC cohort. (G) prognostic prediction performances combination CD68, CD80, for OS our...
<p>Supplementary materials and methods</p>
<p>(A-B) qPCR and ELISA analyses of CCL2 transcriptional secretory levels in the indicated HCC cells. (C-D) Flow cytometry analysis CD80 CD206 expressions THP-1-differentiated macrophages cocultured with cells presence recombinant protein or neutralizing antibody. (E-F) Chemotaxis assays showing effect signaling on SLAMF7-regulated migration using treatments. (G) Left: Gross appearance liver bearing orthotopic tumors treatment groups. Right: The tumor weight volume each group (5 mice...
<p>(A) Immunoblot assays showing the phosphorylated or non-phosphorylated ERK1/2, p38, and JNK proteins in indicated HCC cells. (B) Flow cytometry analyses of CD80 CD206 expressions THP-1-differentiated macrophages cocultured with (C) Chemotaxis effect supernatants from coculture systems on migration abilities macrophages. Scale bar: 100 μm. (D) qPCR ELISA CCL2 transcriptional secretory levels (E) (F) ChIP-qPCR ATF2 binding to gene promoter cell lines SLAMF7 overexpression knockdown....
<p>(A) Immunoblot assay of SHB protein level in the indicated HCC cells. (B-C) assays phosphorylated and non-phosphorylated SHIP1, K63-linked ubiquitinated TRAF6 cells with without silence.</p>
<p>(A) The liver and kidney functions of C57BL/6 mice with orthotopic Hepa1-6 tumors receiving RS102895 anti-PD-1 antibody monotherapy or combination therapy at the study endpoint. (B) Gross appearance bearing Hepa1-6-shSlamf7 in indicated treatment groups. (C) tumor weight volume each group endpoint (5 per group). (D) Hepa1-6-Slamf7 (E) (F) Schematic showing schedule elotuzumab MM HCC subcutaneous tumors. (G) from (H) (I) Volumes during treatment. NS, not significant, ***P<0.001,...
<p>(A) Flow cytometry analyses of CD80 and CD206 expressions in THP-1-differentiated macrophages cocultured with the indicated HCC cells. (B) MHC-II BMDMs (C) qPCR M1 M2 marker genes transcription levels (D-E) Chemotaxis assays showing effect supernatants from coculture systems on migration ability BMDMs. Scale bar: 100 μm. (F) The correlations intra-tumoral SLAMF7 expression CXCL10, CXCL9, ARG1 TCGA-LIHC cohort. (G) prognostic prediction performances combination CD68, CD80, for OS our...
<p>Representative IHC staining images of p53 protein in murine liver tumor tissues the indicated groups. Scale bar: 50 μm.</p>
<p>(A) Representative IHC staining images showing the expressions of SLAMF7, p-STAT1, and p-STAT3 in HCC samples from Fudan LCI cohort. Scale bar: 200 μm (left) 20 (right). (B) immunofluorescence infiltration levels (right) exhausted T cells (CD8+ PD-1+ TCF1-) tumors with high low SLAMF7 protein expression 20μm. *P<0.05, Student’s t test.</p>
<p>Supplementary materials and methods</p>