Analysis of blood immune biomarkers and fecal microbiome in subjects with and without malignant solid tumors: report from a feasibility study

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Background and Objectives: Cytokines and other immune regulatory molecules are critical for mounting an effective immune response against cancer. The gastrointestinal (GI) microbiome plays a significant role in the pathogenesis of cancer and the response to immunotherapy. The central hypothesis guiding this project was that specific immune biomarkers and microbiome profiles will serve as predictors of effective vs. ineffective immunotherapy in patients with malignant diseases. This pilot feasibility study aims to establish baseline immune markers and microbiome profiles in subjects with newly diagnosed malignant solid tumors (n = 10), healthy subjects without diagnosed malignant disease (n = 10), and in existing patients treated with immunotherapy (n = 10). Methods: Parallel blood and stool samples were collected and used in the biomarker and microbiome analysis. The biomarkers in the two groups were analyzed by Principal Component Analysis, heat map with clustering, and differential expression based on P value, and Significance Analysis of Microarrays (SAM). The microbiome analysis was performed using long read 16S rRNA encoding gene sequencing with data visualization and analysis in R. Significant differences in alpha and beta diversity were evaluated between the groups. Results: Several biomarkers that were differentially expressed were identified. Significant taxa differences at the class (Clostridia), order (Clostridiales, Lactobacillillales), family (Eubacteriaceae, Lactobacillaceae), genus and species were identified. Furthermore, a limited analysis of samples from existing patients on immunotherapy who were responders (n = 4) vs. stable non-responders (n = 5) identified differentially expressed immune biomarkers and significant bacterial taxa differences. Conclusion: This study has established the feasibility for conducting a future larger study at the local community cancer center to evaluate whether immune and microbiome markers can predict effective vs. ineffective responses to immunotherapy and whether either or both molecular and microbial markers may have therapeutic potential.