A fascinating 2025 case report is adding to the growing conversation around an emerging application of Hyperbaric Oxygen Therapy (HBOT): it's potential role as an immunosensitising treatment alongside cancer immunotherapy.

Published in Frontiers in Immunology in June 2025, the report describes a patient with an aggressive and rare form of stomach cancer who achieved a complete clinical response after HBOT was added to chemotherapy and immunotherapy.  It provides an intriguing example of how changing the oxygen environment around a tumour might influence the effectiveness of immunotherapy.

The cancer:  hepatoid adenocarcinoma of the stomach

The patient was a 62 year old man diagnosed with hepatoid adenocarcinoma of the stomach (HAS), a rare and particularly aggressive form of gastric cancer.

HAS can behave more aggressively than conventional gastric adenocarcinoma and has a tendency to spread to other parts of the body, including the peritoneum.  It can also respond poorly to immunotherapy.

After initially undergoing surgery and chemotherapy, the patient's cancer unfortunately returned with peritoneal metastases, meaning the disease had reached stage 4.

The patient was then treated with a combination of chemotherapy and an immune checkpoint inhibitor, called sintilimab, a PD-1 inhibitor.

After 4 cycles, however, the result was disappointing.  The cancer had reached 'stable disease', however there had not been a significant reduction in the tumour burden.

Then HBOT was introduced

At this point, the medical team considered whether HBOT could potentially make the existing immunotherapy more effective.

Following the fifth cycle of chemotherapy and immunotherapy, the patient underwent 10 sessions of HBOT for 60 mins at 2.0 ata.  The patient then continued with his sixth cycle of chemotherapy and immunotherapy.

What happened next was remarkable.  Follow up imaging showed complete resolution of the recurrent lesion and peritoneal metastases.

His tumour markers also dramatically changed.  AFP, which had previously been greater than 1,210 ng/mL, fell to 3.06 ng/mL, within the normal range.  Subsequent follow-up showed continued clinical complete response.

A later PET/CT in January 2025 showed no evidence of tumour recurrence, and endoscopic examination showed no active lesions.

Why might oxygen matter?

This is where the study becomes particularly interesting from an HBOT perspective.

Tumours are not simply masses of abnormal cells.  They exist within a complex tumour microenvironment, consisting of blood vessels, immune cells, connective tissue and signalling molecules.

One characteristic of many solid tumours is hypoxia - a low-oxygen environment.  Tumour hypoxia can contribute to an immunosuppressive environment and may make cancer cells more resistant to treatment.

The researchers propose that increasing oxygen availability with HBOT could potentially alter this environment.

1. Reducing tumour hypoxia.  HBOT dramatically increases the amount of oxygen available to tissues.  The researchers suggest that this may reduce hypoxia-related signalling, including activity involving HIF 1-alpha (a protein involved in the cellular response to low oxygen).  Reducing hypoxic signalling may help create an environment that is less favourable to immunosuppressive cells.

2. Potentially improving immune-cell activity.  The paper discusses evidence suggesting HBOT may influence immune-cell behaviour, including the activity of cytotoxic T cells and natural killer (NK) cells.  These are important components of the body's anti-tumour immune response.  The researchers also discuss the possibility that HBOT could enhance signalling pathways involved in immune activation, including the cGAS-STING pathway.

3. Potentially improving the tumour microenvironment.  Tumours often develop abnormal blood vessels that don't function like normal healthy vasculature.  The authors propose that HBOT may help modify this abnormal environment, potentially improving vascular function and allowing immune cells to penetrate the tumour more effectively.  They also discuss whether changes to the extracellular matrix could potentially improve penetration of large therapeutic molecules such as anti-PD-1 antibodies.

In simple terms, the concept is intriguing:

Could increasing oxygen availability make a tumour's environment more receptive to the immune system and therefore make immunotherapy work better?

This is the key idea behind this paper.  Rather than suggesting that HBOT itself is a cancer treatment, the researchers propose that HBOT could potentially act as an immunosensitising therpay.

The researchers note that the abnormal vasculature-hypoxia-immunosuppression relationship is not unique to hepatoid adenocarcinoma and may occur in other advanced gastric cancers as well.

This is one case study, however it demonstrates an exciting concept:

Oxygen may influence much more than oxygen delivery.  It may also influence the cellular and immune environment in which disease occurs.  Could modifying tumour oxygenation help the immune system work more effectively against cancer?

Future clinical trails may give more insight in space.

Reference: Li W, Wei J, Zhang P, et al.  Hyperbaric oxygen therapy as an immunosensitizing strategy in advanced gastric hepatoid adenocarcinoma:  a case report.  Frontiers in Immunology.  2025.