Innate-like lymphocyte regulation of host-microbiota interactions in cancer

点击翻译按钮获取中文摘要

PROJECT ABSTRACT Host-microbe interactions profoundly impact cancer. This is exemplified by well-documented infections that promote cancer, and the ability to prevent these cancers through vaccination or pathogen avoidance. However, humans are densely colonized with trillions of normally beneficial microbes, termed the microbiota, which also have the ability to promote cancers through the induction of inflammation or genomic instability. Further, recent seminal studies demonstrated that intestinal microbiota are also required for anti-tumor immunity in the context of therapeutic interventions, such as checkpoint blockade. Despite these advances, the specific pathways by which microbiota shape pro- versus anti-tumor immunity remain poorly defined, and the potential relevance of these findings to specific types of cancer are unknown. The fundamental focus of supplemental application is to support training of a graduate student candidate who will interrogate the role of innate-like lymphocytes in shaping host-microbiota interactions that protect from tumor progression and promote the efficacy of immunotherapies in colorectal cancer (CRC). This will be an outstanding opportunity for the candidate to grow as an independent scientist and test the proposed novel hypotheses that are directly relevant to the parent R01 for this proposal. Expected outcomes are for this candidate to be highly successful in embedding within the scientific community, executing the proposed experiments, and analyzing data that could provoke a paradigm shift in our understanding of how interactions between immune cells and the intestinal microbiota shape colorectal cancer induction, progression, or immunotherapy response.