Project 2

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PROJECT SUMMARY U.S. Blacks have the highest mortality rate of colorectal cancer of any ethnic group in the country. To achieve colon cancer health equity, it is critical to determine the underlying biological factors associated with poorer colon cancer outcomes in Blacks, which could lead to tailored prevention and intervention approaches. The gut microbiota may play an important biologic role in racial disparities for colon cancer outcomes. Increasing evidence indicates that the gut microbiota influences innate and adaptive immune function in the tumor microenvironment. The tumor immune microenvironment is critical for the detection and destruction of nascent tumor cells. Our preliminary data suggest that healthy Blacks have a significantly different gut microbiome compared to Whites; importantly, we showed that these gut bacteria are further altered in colon cancer patients, supporting our hypothesis. Our animal experiments further suggest that gut bacteria modulate tumor immune microenvironment and affect the efficiency of cancer response to therapy. However, no studies have examined the relationship between the broader human microbiome, tumor immune microenvironment, and outcomes of colon cancer in the comparative research setting with Blacks and Whites. Our overarching goal is to achieve colon cancer health equity, by elucidating gut microbial factors associated with poorer colon cancer outcomes in Blacks. Our specific aims are 1) to identify gut bacteria associated with racial disparity in colon cancer and its recurrence, using full genome shotgun sequencing microbiome assay in 200 Black and 200 White colon cancer patients (Stage I-III); 2) to determine how the immune system mediates the microbiome’s effect on colon cancer disparity, using immunophenotyping assay, from 30-parameter flow cytometry, and neoantigen load, from whole exome sequencing, in tumors of 50 Black and 50 White colon cancer patients. This first microbiome study of colon cancer disparities will comprehensively investigate the gut microbiome and its role in shaping the tumor immune microenvironment. This project will help to achieve colon cancer health equity by generating novel information about the role of the microbiome in colon tumorigenesis and progression. Knowledge gained from this study may improve our ability to identify people at high risk of recurrence, particularly in Blacks. The new information may further lead to the development of tailored approaches to prevention and therapeutics that exploit microbially-driven immune responses in colon cancer.