Journal: Cancer Research

Article Title: Nerves Stimulate Cross-talk Between Gastric Cancer and Group 3 Innate Lymphoid Cells to Enhance Immunosuppression

doi: 10.1158/0008-5472.CAN-25-3092

Figure Lengend Snippet: IL22 upregulates PD-L1 expression in gastric cancer cells through the UPR IRE1α–XBP1 axis. A, mIF images show the alterations of PD-L1 + tumor cells (purple), CD4 + (green), and CD8 + (red) T cells in orthotopic gastric cancer tumors from control and Abhd16a -knockdown mice following IL22 treatment. Scale bar, 50 μm. B, KEGG pathway enrichment analysis of RNA-seq data of gastric cancer tissues with or without IL22 treatment. C, RT-PCR was used to assess the mRNA expression of key downstream molecules of the UPR branches ( XBP1 , ATF4 , ATF6 ) in control and IL22RA1 -knockdown gastric cancer cells. D, Western blotting analysis of PD-L1 and XBP1s levels in control and IL22RA1 -knockdown MGC-803 cells treated with IL22 (100 μg/L). E, Western blotting detection of PD-L1 and XBP1s levels in XBP1- knockdown MGC-803 cells treated with IL22 and MGC-803 cells treated with IL22 or XBP1s inhibitor (STF083010, 30 μmol/L) in combination with IL22. F, The binding sequence of XBP1 on the CD274 promoter. G and H, ChIP ( G ) and luciferase reporter assay ( H ) showing the transcriptional regulation of CD274 by XBP1s under IL22 stimulation. I, Orthotopic gastric cancer mouse models ( n = 5 per group) were injected with anti-IL22 (200 μg per mouse), anti-CD90.2 antibody (150 μg per mouse), anti-CD90.2 antibody in combination with IL22 (500 ng per mouse), or anti-CD90.2 antibody in combination with XBP1s inhibitors (STF083010, 30 mg/kg) and IL22 for 2 weeks. IHC analysis was used to show IL22, XBP1s, and PD-L1 levels in gastric cancer tissues. Scale bar, 200 μm. J, Tumor volume of orthotopic gastric cancer models under treatments the same as in I . *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, nonsignificant.

Article Snippet: For the animal experiment, LysoPS (2.5 mg/kg, Sigma, 858144P), GPR34 inhibitor (GPR34 receptor antagonist 2, 20 mg/kg, MERYER, 907952), AKT inhibitor (perifosine, 20 mg/kg, MedChemExpress, HY-50909), XBP1s inhibitor (STF-083010, 30 mg/kg, MedChemExpress, HY-15845), IL22 Monoclonal Antibody (200 μg/mouse, eBioscience, 16-7222-82, RRID: AB_2016695), rmIL22 (500 ng/mouse, ABclonal, RP02942), and CD90.2 (150 μg/mouse, BioXCell, BE0066, RRID: AB_1107682) for ILC3 depletion were intraperitoneally injected once every 3 days.

Techniques: Expressing, Control, Knockdown, RNA Sequencing, Reverse Transcription Polymerase Chain Reaction, Western Blot, Binding Assay, Sequencing, Luciferase, Reporter Assay, Injection

Journal: Cancer Research

Article Title: Nerves Stimulate Cross-talk Between Gastric Cancer and Group 3 Innate Lymphoid Cells to Enhance Immunosuppression

doi: 10.1158/0008-5472.CAN-25-3092

Figure Lengend Snippet: Combination therapy enhances the anti–PD-L1 immunotherapeutic effect in gastric cancer. A and B, After tumor formation, the orthotopic gastric cancer mice ( n = 5 per group) were treated with anti–PD-L1 (100 μg per mouse), GPR34 inhibitor (20 mg/kg), or XBP1s inhibitor (30 mg/kg) every 3 days or ACh inhibitor (2.5 mg/kg) daily. Combinations of anti–PD-L1 with each inhibitor followed the every 3-day dosing schedule for a total duration of 2 weeks via i.p. injection. Living images were used to monitor tumor progression at 5-day intervals from the time of drug administration ( A ); IHC and mIF were performed to detect PD-L1 and XBP1s levels and proportions of CD4 + (green) and CD8 + (red) T cells in gastric cancer tissues at the end of treatments ( B ). Scale bars, 1.000e+5 –∼ 5.000e + 5 p/s/cm 2 /sr for living images; 200 μm for IHC; 50 μm for immunofluorescence. C and D, Representative images ( C ) and tumor volume ( D ) of subcutaneous tumors. The administration protocol for the mice was consistent with the description provided in A and B . **, P < 0.01; ***, P < 0.001.

Article Snippet: For the animal experiment, LysoPS (2.5 mg/kg, Sigma, 858144P), GPR34 inhibitor (GPR34 receptor antagonist 2, 20 mg/kg, MERYER, 907952), AKT inhibitor (perifosine, 20 mg/kg, MedChemExpress, HY-50909), XBP1s inhibitor (STF-083010, 30 mg/kg, MedChemExpress, HY-15845), IL22 Monoclonal Antibody (200 μg/mouse, eBioscience, 16-7222-82, RRID: AB_2016695), rmIL22 (500 ng/mouse, ABclonal, RP02942), and CD90.2 (150 μg/mouse, BioXCell, BE0066, RRID: AB_1107682) for ILC3 depletion were intraperitoneally injected once every 3 days.

Techniques: Injection, Immunofluorescence

Journal: Oncology Letters

Article Title: Schisandrin B suppresses cholangiocarcinoma by targeting the ROS/p38 MAPK/NF-κB axis

doi: 10.3892/ol.2026.15551

Figure Lengend Snippet: Sch B induced a dose-dependent increase in ROS levels in CCA cells. (A) BIP, (B) CHOP and (C) XBP1s expressions were determined by reverse-transcription quantitative PCR in CCA cells treated with different concentrations of Sch B (0, 10, 20, 40, 80, 160 µmol/l), (D) BIP, CHOP and XBP1s expression levels were determined by western blotting in CCA cells treated with different concentrations of Sch B (0, 40, 80, 160 µmol/l). (E) ROS levels in CCA cells treated with different concentrations of Sch B (0, 40, 80, 160 µmol/l) were measured using the ROS probe DCFH-DA. (F) Flow cytometry analysis of ROS levels in CCA cells following treatment with various Sch B concentrations (0, 40, 160 µmol/l). Statistical analysis was performed using ANOVA and Dunnett's post hoc test. *P<0.05, **P<0.01, ***P<0.001. CCA, cholangiocarcinoma; Sch B, Schisandrin B; Ctrl, control; ROS, reactive oxygen species.

Article Snippet: XBP1s , 12782 , 1:1,000 , Cell Signaling Technology, Inc..

Techniques: Reverse Transcription, Real-time Polymerase Chain Reaction, Expressing, Western Blot, Flow Cytometry, Control

Journal: Oncology Letters

Article Title: Schisandrin B suppresses cholangiocarcinoma by targeting the ROS/p38 MAPK/NF-κB axis

doi: 10.3892/ol.2026.15551

Figure Lengend Snippet: NAC counteracted the upregulatory effect of Sch B on ROS expression. After treatment with 160 µmol/l Sch B + different concentrations of NAC (0, 0.5, 1, 3, 6 µmol/l). BIP, CHOP and XBP1s expression determined by (A) western blotting and (B) reverse transcription-quantitative PCR in CCA cells. (C) LDH activity in cell culture medium. (D) Cell activity levels detected by the Calcein AM-PI live cell staining. (E) Western blot analysis of the expression levels of Bax in CCA cells. Statistical analysis was performed using ANOVA and Dunnett's post hoc test. **P<0.01, ***P<0.001. ROS, reactive oxygen species; CCA, cholangiocarcinoma; NAC, N-acetyl-L-cysteine; ctrl, control; Sch B, Schisandrin B; LDH, lactate dehydrogenase.

Article Snippet: XBP1s , 12782 , 1:1,000 , Cell Signaling Technology, Inc..

Techniques: Expressing, Western Blot, Reverse Transcription, Real-time Polymerase Chain Reaction, Activity Assay, Cell Culture, Staining, Control