Isolated gut microbe drives stronger responses to cancer therapy

The National Cancer Center Research Institute in Tokyo reports that a newly isolated gut bacterium, designated Hominenteromicrobium strain YB328, mobilizes specialized dendritic cells to strengthen the impact of PD-1 blockade immunotherapy across several tumor types.

Patients carrying this strain in their intestines showed more robust infiltration of activated T cells in tumors and experienced longer progression-free survival after immune checkpoint treatment.

Immune checkpoint blockade therapies, including monoclonal antibodies targeting PD-1 and PD-L1, have become standard options for many cancer types and have led to significant improvements in progression-free survival and overall survival.

In gut microbiota, the abundance of bacteria such as Ruminococcus spp. and Prevotellaceae spp. has been previously associated with the clinical efficacy of immune checkpoint blockade therapies, while other taxa have shown links to shorter progression-free survival.

Several mechanisms have been proposed to explain how gut microbes exert these effects, including stimulation of macrophages and monocytes, antigenic mimicry between microbiota and tumor antigens, and direct activation of tumor-infiltrating CD8⁺ T cells by microbiota-derived metabolites.

Predictive biomarkers capable of identifying patients most likely to respond remain scarce, leaving an urgent need for new strategies to broaden the impact of immunotherapy.

In the study, “Microbiota-driven antitumour immunity mediated by dendritic cell migration,” published in Nature, researchers isolated a previously undescribed bacterial strain to investigate whether its presence augments the antitumor efficacy of PD-1 blockade therapy.

Stool samples were prospectively collected from 50 Japanese patients, including 15 individuals with non-small cell lung cancer and 35 with gastric cancer, all treated with PD-1 blockade therapy.

Researchers performed 16S rRNA gene amplicon sequencing on fecal samples to assess bacterial composition and used receiver operating characteristic analysis, a sensitivity/specificity analysis, to evaluate predictive biomarkers. Principal coordinate analysis and analysis of similarities measured differences in microbiota between responders and non-responders.

Researchers first identified that members of the family Ruminococcaceae were significantly enriched in responders and correlated with prolonged progression-free survival. Strain YB328 was isolated from the feces of patients who responded to therapy, followed by metagenome sequencing and species-level quantification using Kraken2 and Bracken.

Germ-free and antibiotic-treated mice were colonized with fecal microbiota transplantation and monitored for tumor growth after anti-PD-1 monoclonal antibody treatment.

Patients with a high abundance of YB328 in fecal samples exhibited significantly longer progression-free survival and increased infiltration of CD103⁺ CD11b⁻ conventional dendritic cells in tumors across a range of cancer types.

YB328 isolated from these responders’ previous fecal samples augmented the antitumor efficacy of PD-1 blockade treatment in a mouse model.

Separate analyses showed that mice colonized with YB328 demonstrated an increased abundance of activated CD8⁺ T cells, cytokine-producing CD8⁺ T cells, and a diverse T cell receptor repertoire in tumor-infiltrating lymphocytes.

In in vitro studies, YB328-treated dendritic cells displayed higher expression of CD86, CD80, major histocompatibility class I molecules, and other co-stimulatory markers. This dendritic cell phenotype corresponded with increased induction of PD-1 expression and expanded reactivity of CD8⁺ T cells against tumor antigens.

Administration of a different microbe, P. vulgatus, was associated with shorter progression-free survival in patients and reduced accumulation of PD-1⁺ CD8⁺ T cells in mouse tumors. Additional experiments demonstrated that co-administration of P. vulgatus abolished the antitumor effects observed with YB328 treatment alone.

In contrast to previous reports, the abundance of the genera Faecalibacterium, Enterococcus, Bifidobacterium and Akkermansia did not differ significantly between responders and non-responders.

Researchers conclude that YB328 colonization promotes the differentiation and migration of CD103⁺ CD11b^– conventional dendritic cells, which activate tumor-infiltrating CD8⁺ T cells and enhance the efficacy of PD-1 blockade therapies.

Authors propose targeting the gut microbiota could create new approaches for improving immunotherapy outcomes in patients with diverse cancer types.

© 2025 Science X Network

The National Cancer Center Research Institute in Tokyo reports that a newly isolated gut bacterium, designated Hominenteromicrobium strain YB328, mobilizes specialized dendritic cells to strengthen the impact of PD-1 blockade immunotherapy across several tumor types.

Patients carrying this strain in their intestines showed more robust infiltration of activated T cells in tumors and experienced longer progression-free survival after immune checkpoint treatment.

Immune checkpoint blockade therapies, including monoclonal antibodies targeting PD-1 and PD-L1, have become standard options for many cancer types and have led to significant improvements in progression-free survival and overall survival.

In gut microbiota, the abundance of bacteria such as Ruminococcus spp. and Prevotellaceae spp. has been previously associated with the clinical efficacy of immune checkpoint blockade therapies, while other taxa have shown links to shorter progression-free survival.

Several mechanisms have been proposed to explain how gut microbes exert these effects, including stimulation of macrophages and monocytes, antigenic mimicry between microbiota and tumor antigens, and direct activation of tumor-infiltrating CD8⁺ T cells by microbiota-derived metabolites.

Predictive biomarkers capable of identifying patients most likely to respond remain scarce, leaving an urgent need for new strategies to broaden the impact of immunotherapy.

In the study, “Microbiota-driven antitumour immunity mediated by dendritic cell migration,” published in Nature, researchers isolated a previously undescribed bacterial strain to investigate whether its presence augments the antitumor efficacy of PD-1 blockade therapy.

Stool samples were prospectively collected from 50 Japanese patients, including 15 individuals with non-small cell lung cancer and 35 with gastric cancer, all treated with PD-1 blockade therapy.

Researchers performed 16S rRNA gene amplicon sequencing on fecal samples to assess bacterial composition and used receiver operating characteristic analysis, a sensitivity/specificity analysis, to evaluate predictive biomarkers. Principal coordinate analysis and analysis of similarities measured differences in microbiota between responders and non-responders.

Researchers first identified that members of the family Ruminococcaceae were significantly enriched in responders and correlated with prolonged progression-free survival. Strain YB328 was isolated from the feces of patients who responded to therapy, followed by metagenome sequencing and species-level quantification using Kraken2 and Bracken.

Germ-free and antibiotic-treated mice were colonized with fecal microbiota transplantation and monitored for tumor growth after anti-PD-1 monoclonal antibody treatment.

Patients with a high abundance of YB328 in fecal samples exhibited significantly longer progression-free survival and increased infiltration of CD103⁺ CD11b⁻ conventional dendritic cells in tumors across a range of cancer types.

YB328 isolated from these responders’ previous fecal samples augmented the antitumor efficacy of PD-1 blockade treatment in a mouse model.

Separate analyses showed that mice colonized with YB328 demonstrated an increased abundance of activated CD8⁺ T cells, cytokine-producing CD8⁺ T cells, and a diverse T cell receptor repertoire in tumor-infiltrating lymphocytes.

In in vitro studies, YB328-treated dendritic cells displayed higher expression of CD86, CD80, major histocompatibility class I molecules, and other co-stimulatory markers. This dendritic cell phenotype corresponded with increased induction of PD-1 expression and expanded reactivity of CD8⁺ T cells against tumor antigens.

Administration of a different microbe, P. vulgatus, was associated with shorter progression-free survival in patients and reduced accumulation of PD-1⁺ CD8⁺ T cells in mouse tumors. Additional experiments demonstrated that co-administration of P. vulgatus abolished the antitumor effects observed with YB328 treatment alone.

In contrast to previous reports, the abundance of the genera Faecalibacterium, Enterococcus, Bifidobacterium and Akkermansia did not differ significantly between responders and non-responders.

Researchers conclude that YB328 colonization promotes the differentiation and migration of CD103⁺ CD11b^– conventional dendritic cells, which activate tumor-infiltrating CD8⁺ T cells and enhance the efficacy of PD-1 blockade therapies.

Authors propose targeting the gut microbiota could create new approaches for improving immunotherapy outcomes in patients with diverse cancer types.

© 2025 Science X Network