Japanese Study Reveals Gut Microbe YB328 Boosts PD-1 Therapy Response, Addressing 80% Non-Response Rate

Researchers at the National Cancer Center in Tokyo have identified a novel gut bacterium, Hominenteromicrobium strain YB328, that significantly enhances the effectiveness of PD-1 blockade immunotherapy in cancer patients. This breakthrough, recently published in the journal Nature on July 14, 2025, offers a potential solution to improve outcomes for the approximately 80% of patients who currently do not respond effectively to these advanced cancer treatments. The discovery underscores the growing understanding of the gut microbiome's profound influence on the body's immune responses to cancer.

The study revealed that patients with higher levels of Hominenteromicrobium strain YB328 in their gut microbiota exhibited stronger tumor infiltration by activated T cells and experienced significantly longer progression-free survival. As announced by Dr. Singularity, "> Experiments in mice confirmed that YB328 promotes the activation and migration of specific dendritic cells, which boost the immune response against tumors during PD-1 therapy." These specialized dendritic cells play a pivotal role in priming the immune system to recognize and attack cancer cells more effectively, thereby amplifying the therapeutic impact of PD-1 inhibitors.

The comprehensive findings are based on prospective studies involving 50 Japanese cancer patients, specifically those with non-small cell lung cancer and gastric cancer, who were undergoing PD-1 blockade therapy. Further validation was conducted through rigorous experiments in mouse models. Notably, the research also highlighted that another gut microbe, P. vulgatus, was associated with shorter progression-free survival in patients and could negate YB328's beneficial effects when co-administered. This contrasts with some prior research, as the study found no significant correlation between the abundance of Faecalibacterium, Enterococcus, Bifidobacterium, or Akkermansia and treatment response in this specific cohort.

The identification of Hominenteromicrobium strain YB328 presents a promising avenue for both a predictive biomarker and a novel therapeutic target in cancer immunotherapy. Current immune checkpoint inhibitors, while revolutionary for some, have limited response rates, making this discovery particularly impactful. The research team, led by immunologist Dr. Hiroyoshi Nishikawa, dedicated approximately 18 months to isolating and characterizing this specific microorganism. Building on these results, plans are now actively being developed to initiate human clinical trials within the next three years, aiming to translate these findings into broader clinical benefits for cancer patients worldwide.