Microbiome as a Predictive Biomarker

Creative Biolabs is here to provide you with a comprehensive introduction to the impact of the microbiome on the host immune system, particularly in the process of immune checkpoint blockade, and provide theoretical support in order to facilitate your selection and exploration of rational pathways that enhance immunotherapeutic efficacy while concurrently mitigating toxicity.

Microbiome and Immune Regulation

The composition and population diversity of the symbiotic gut microbiota have various effects on the immune system, and their impact on ICB tumor intervention and autoimmune side effect spectrum has been partially elucidated:

Mice receiving fecal microbiota transplantation can improve tumor control, enhance T cell response, and enhance the effectiveness of anti-PD-L1 intervention.
Melanoma patients receiving ICB exhibit significant diversity and compositional differences in their gut microbiota.
Disruption of the gut microbiota through antibiotic treatment adversely affects the response to ICB in mouse models.
Oral administration of Bifidobacterium can induce anti-tumor response and synergistic effects with PD-1 antibody treatment.
Epithelial cancer patients enriched with Akkermansia species show better responses to IBD intervention.

Fig 1. A certain correlation between patients' microbiome and the effect of anti-PD-L1.¹

Opportunities and Challenges

The relationship between ICB response variability and symbiotic gut microbiota has been validated by numerous experiments. However, further prospective research is still needed for its effective and safe application. Currently, the use of gut microbiota as an intervention and prediction tool still faces the following challenges:

Lack of unified and standardized gut microbiota sampling and analysis platforms.
Regional heterogeneity of microbial communities and introduction of more potential confounding factors through antibiotic use.
Effective fecal microbiota transplantation and antibiotic regimens are still in the early exploration stage.

Research Status

Title: Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Research Objective:

Characterize the correlation between gut microbiome and tumor response to ICB in human cancer patients.

Methodology:

Perform metagenomic and relative abundance analysis of gut and oral microbiome in melanoma patients receiving anti-PD-1 immunotherapy to characterize their diversity and composition.

Research Findings:

Patients with high gut microbiome diversity in the fecal microbiome exhibit significant prolongation of progression-free survival. Patients responding to immune suppression measures have higher α-diversity and relative abundance of bacteria from Ruminococcaceae, along with enrichment of synthetic metabolic pathways and functional differences. These results demonstrate the potential involvement and regulation of the gut microbiome in the response of melanoma patients to PD-1 immunotherapy.

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