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 宿主与微生物的相互作用对癌症产生深远的影响。有据可查的感染证明了这一点 促进癌症，以及通过疫苗接种或避免病原体来预防这些癌症的能力。然而， 人类密集地居住着数万亿种通常有益的微生物，称为微生物群，也称为微生物群。 具有通过诱导炎症或基因组不稳定性促进癌症的能力。此外，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 治疗干预措施，例如检查点封锁。尽管取得了这些进展，但具体途径 哪种微生物群形成促肿瘤免疫和抗肿瘤免疫仍然不明确，以及潜在的相关性 这些发现对于特定类型的癌症尚不清楚。补充申请的根本重点 是为了支持对研究生候选人的培训，他们将质疑类先天的作用 淋巴细胞塑造宿主-微生物群相互作用，防止肿瘤进展并促进 免疫疗法在结直肠癌（CRC）中的疗效。这将是一个绝佳的机会 候选人成长为一名独立科学家并测试直接提出的新假设 与本提案的父 R01 相关。预期结果是该候选人非常成功 融入科学界、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如何相互作用的理解的范式转变 肠道微生物群影响结直肠癌的诱导、进展或免疫治疗反应。