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

癌症中宿主-微生物群相互作用的先天性淋巴细胞调节

• 批准号: 10815434
• 负责人: Gregory F Sonnenberg
• 金额: $ 13.46万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10815434
• 关键词: Cells; Cessation of life; Colorectal Cancer; Communities; Data; Genomic Instability; Health Care Costs; Human; Immune; Immune checkpoint inhibitor; Immunotherapy; Infection; Inflammation; Lymphocyte; Malignant Neoplasms; Newly Diagnosed; Outcome; Parents; Pathway interactions; Regulation; Role; Scientist; Seminal; Shapes; Testing; Therapeutic Intervention; Training Support; Tumor Immunity; Tumor Promotion; United States; Vaccination; beneficial microorganism; cancer type; carcinogenesis; experimental study; graduate student; gut microbiota; host microbiota; host-microbe interactions; immune checkpoint blockade; improved; microbiota; novel; novel strategies; pathogen; prevent; response; socioeconomics; tumor progression

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.

项目摘要 宿主-微生物相互作用深刻影响癌症。这是一个很好的例子， 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，在这方面， 人类密集地寄居着数万亿通常有益的微生物，称为微生物群， 具有通过诱导炎症或基因组不稳定性来促进癌症的能力。此外，最近 开创性的研究表明，肠道微生物群也是抗肿瘤免疫所必需的， 治疗干预，如检查点封锁。尽管取得了这些进展， 哪种微生物群形状的促肿瘤免疫与抗肿瘤免疫仍然不清楚， 这些发现对特定类型的癌症是未知的。补充申请的基本焦点 是为了支持研究生候选人的培训， 淋巴细胞在塑造宿主-微生物群相互作用中的作用， 免疫疗法在结直肠癌（CRC）中的疗效。这将是一个绝佳的机会， 候选人成长为一个独立的科学家，并测试提出的新假设，直接 与本提案的父R 01相关。预期结果是该候选人非常成功 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细胞之间相互作用的理解的范式转变。 肠道微生物群塑造结直肠癌诱导、进展或免疫治疗反应。