New research has revealed how a widely-used probiotic may enhance immune responses in some patients when given alongside cancer immunotherapy.
Researchers at Cardiff University, working in partnership with Kumamoto University in Japan, have provided the first clear biological explanation for earlier clinical reports that the probiotic Clostridium butyricum MIYAIRI 588 - known as CBM588 - can enhance the body's immune response against some cancers.
The link between the gut microbiome and outcomes for patients with cancer has been of interest for over a decade.
Dr Garry Dolton, Cardiff University School of Medicine, said: "Several recent studies have shown that the gut microbiome is linked to how well patients respond to checkpoint blockade therapy, which allows immune cells called T-cells to recognise and destroy tumours. This has raised interest in strategies to harness probiotics to improve immune responses during cancer treatment."
The CBM588 probiotic has been used in Japan since the 1960s to treat gastrointestinal disturbances, and has a long-established safety record including use in young children and during pregnancy. More recently, it has been reported to improve response rates and overall survival in patients receiving immune checkpoint inhibitor therapy (ICI) for non-small cell lung cancer and metastatic renal cell carcinoma. Despite these very encouraging clinical observations, the biological mechanism for this effect has remained unclear.
In the new study, the researchers used blood samples from healthy donors and lung cancer patients to demonstrate the impact of the CBM588 probiotic on a specialised population of T-cells called Vγ9Vδ2 T-cells, which can recognise and kill cancer cells.
Professor Chihiro Motozono, from Kumamoto University and the lead author of the study, said: "Our colleagues in Kumamoto observed encouraging clinical results with CBM588, but the key question was how it was benefiting patients.
"By combining carefully characterised clinical samples in Japan with mechanistic immunology expertise in Cardiff, we identified a specific immune cell population that is activated in patients receiving CBM588. In laboratory studies, this population can expand and recognise cancer cells, and in patient samples, its activation was associated with improved clinical outcomes."
The researchers found that CBM588 activated a specialised group of immune cells known as Vγ9Vδ2 T-cells. In laboratory experiments, exposure to the probiotic led to expansion of this cell population, which includes cells capable of recognising and killing cancer cells. In blood samples from lung cancer patients, higher activation of these cells was associated with improved treatment outcomes.
Professor Andrew Sewell, Cardiff University, added: "This study moves us from an association between the gut microbiome and cancer treatment outcomes to a defined immune pathway. By identifying a measurable biomarker linked to patient outcomes, we can now design more rational, evidence-based clinical trials."
Our findings do not mean probiotics cure cancer, but give a deeper understanding of how probiotics like CBM588 could be given in addition to standard immunotherapy to improve and support better treatment outcomes for patients.
The team stresses that the clinical analyses to date are modest in size, and further prospective trials will be needed to confirm these findings and determine which patients are most likely to benefit.
This work was supported by AMED Research Programs, the Wellcome Trust and Cancer Research Wales. The work coincides with new funding from Cancer Research Wales to further investigate the mechanism and optimise how microbiome-based approaches might be integrated into cancer treatment.
The research, A probiotic bacterium modulates antitumor γδ T-cell responses in lung cancer, was published in Frontiers in Immunology.
