Hyperbaric oxygen facilitates teniposide-induced cGAS-STING activation to enhance the antitumor efficacy of PD-1 antibody in HCC.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro cell culture and in vivo mouse models without human clinical data.
PubMed 36002188 · doi:10.1136/jitc-2021-004006
What was done
Human hepatocellular carcinoma (HCC) cells were treated with chemotherapy agents (teniposide and oxaliplatin) under hypoxic, normoxic, or reoxygenated conditions to evaluate cGAS-STING pathway activation. In vivo, orthotopic liver mouse tumor models and other mouse models were treated with teniposide or oxaliplatin with or without hyperbaric oxygen (HBO) therapy, alongside anti-PD-1 antibody treatment, to assess changes in the tumor microenvironment and antitumor efficacy.
What was found
Teniposide stimulated greater cGAS-STING signaling in human HCC cells than oxaliplatin. In vitro hypoxia inhibited teniposide-induced cGAS-STING signaling via hypoxia-inducible factor 1α, which was reversed upon reoxygenation. In vivo, HBO combined with teniposide enhanced type I interferon and NF-κB signaling, stimulated dendritic cells and cytotoxic T cells, and improved tumor response to anti-PD-1 therapy. The abstract reports no numerical values, effect sizes, or statistical significance metrics.
Why it matters
Tumor hypoxia commonly suppresses cGAS-STING activation and limits immunotherapy response in HCC. Combining hyperbaric oxygen with teniposide represents a potential strategy to relieve hypoxia-mediated immune evasion and sensitize solid tumors to checkpoint inhibitors.
Limits
The study is entirely preclinical, relying on cell cultures and mouse models; human clinical efficacy and safety remain unproven. Specific sample sizes, tumor volume metrics, survival rates, and statistical parameters are omitted from the abstract.
Cited by
- supports Hyperoxygenation enhances T-cell metabolism and infiltration, reduces PD-L1 expression, and improves the efficacy of immune checkpoint inhibitor therapy.