Hyperbaric Oxygen Boosts PD-1 Antibody Delivery and T Cell Infiltration for Augmented Immune Responses Against Solid Tumors

Aberrant mechanical properties and immunosuppression are the two key factors that limit the antitumor efficacy of T cell immune checkpoint blockade inhibitors, e.g., programmed cell death-1 antibody (PD-1 Ab), against solid tumors in the clinic. This study leverages hyperbaric oxygen (HBO) for the first time to address these two issues and reports the PD-1-Ab-mediated immune responses against various stroma-rich solid malignancies. The results demonstrate that HBO promoted PD-1 Ab delivery and T cells infiltration into tumor parenchyma by depleting the extracellular matrix's main components, such as collagen and fibronectin. Furthermore, HBO disrupts hypoxia-mediated immunosuppression and helps PD-1 Ab trigger robust cytotoxic T lymphocytes and long-lasting immunological memory to inhibit tumor relapses. Such enhanced immune responses are effective in solid tumors from rodents and the cancer cells from hepatocellular carcinoma patients. The results illustrate that HBO bolsters antitumor efficacy of PD-1 Ab, and the HBO-PD-1 Ab combination is a promising stroma-rich solid tumors' treatment in the clinic.

Automated summary

This study utilized hyperbaric oxygen (HBO) to overcome mechanical and immunosuppressive limitations of T cell immune checkpoint inhibitors, such as PD-1 Ab, against solid tumors. HBO enhanced PD-1 Ab delivery and T cell infiltration, disrupting immunosuppression and promoting robust immune responses to inhibit tumor relapses. Such enhanced efficacy was observed in solid tumors in rodents and hepatocellular carcinoma patients, highlighting the potential of HBO-PD-1 Ab combination therapy in stroma-rich solid tumors.