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. 2022 Aug 24;10(8):e004006. doi: 10.1136/jitc-2021-004006

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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HBO facilitated teniposide to induce cGAS-STING signaling in mouse HCC tumor model. (A) Schematic illustration of the tumor microenvironment survey experiments in mouse HCC tumor model. Hepa1-6 liver orthotopically tumor-bearing mice were intraperitoneally injected with DMSO (Ctrl), oxaliplatin (10 mg/kg) and teniposide (10 mg/kg) twice at indicated time points. HBO therapy was administrated alone or after chemotherapy for a total of five times (n=3 per group). Tumors were resected and weighed after the final HBO administration. (B–C) HIF-1α expression of mice tumor tissues was determined by immunohistochemical staining (B) and immunoblotting (C) after HBO administration. Scale bars: 50 µm. (D) p-IRF3 expression of mice tumor tissues from different treatment groups was determined by immunohistochemical staining. Scale bars: 50 µm. (E) Ifn-b, Ccl5 and Cxcl10 mRNA expression of mice tumor tissues from different treatment groups was detected by RT-qPCR. (F) Representative images and quantitative analysis of p-IRF3^low (n=60) and p-IRF3^high (n=60) staining in tumor tissues from 120 patients with HCC. Scale bars: 50 µm (upper) and 25 µm (lower). (G) Disease-free survival (left) and overall survival (right) analyses of 120 patients with HCC showed a positive correlation between high p-IRF3 expression level and favorable prognosis. The prognostic significance was assessed by Cox regression analysis. (H–I) Kaplan–Meier curves were generated from the public microarray databases of human patients using an online software (kmplot.com/analysis/). Low expression levels of HIF1A (H) and high expression levels of IFN-B1, CCL5 and CXCL10 (I) were positively correlated with better survival of patients with HCC. Data in (C) are representative of three independent experiments. Data in (E) are shown as mean±SD of three independent experiments. *P<0.05, **P<0.01, ***P<0.001. cGAS-STING, cyclic GMP-AMP synthase-stimulator of interferon genes; Ctrl, control; HBO, hyperbaric oxygen; DMSO, Dimethyl sulfoxide; HCC, hepatocellular carcinoma; HIF-1α, hypoxia inducible factor 1α; IRF3, interferon regulatory factor 3; Oxa, oxaliplatin; Rel. expression, relative expression; RT-qPCR, real time quantitative PCR; Teni, teniposide.