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

项目摘要 宿主-微生物的相互作用对癌症产生了深远的影响。这一点以有充分记录的感染为例 促进癌症，以及通过接种疫苗或避免病原体来预防这些癌症的能力。然而， 人类密集地栖息着数以万亿计的正常有益的微生物，被称为微生物区系，它也 有能力通过诱导炎症或基因组不稳定来促进癌症。更进一步，最近 开创性研究表明，肠道微生物群也是抗肿瘤免疫所必需的。 例如检查站封锁等治疗性干预措施。尽管取得了这些进展，但通过 哪种微生物区系形态的亲肿瘤免疫和抗肿瘤免疫仍未明确，以及 这些发现对特定类型的癌症是未知的。补充适用的基本着力点 是为了支持对研究生候选人的培训，他们将询问天生的角色 淋巴细胞在塑造防止肿瘤进展和促进肿瘤进展的宿主-微生物群相互作用中的作用 免疫疗法在结直肠癌中的疗效。这将是一个难得的机会 候选人成长为一名独立的科学家，并测试提出的新假设，这些假设直接 与此方案的父R01相关。预期的结果是这位候选人非常成功 在嵌入科学界，执行拟议的实验，并分析数据， 可能会引发我们对免疫细胞和免疫细胞之间相互作用的理解的范式转变 肠道微生物区系形态对结直肠癌的诱导、进展或免疫治疗反应。

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.