Gut Microbiome and Cancer Immunotherapy Outcomes in Advanced Renal Cell Carcinoma

晚期肾细胞癌的肠道微生物组和癌症免疫治疗结果

基本信息

批准号：
10579285
负责人：
Mehmet Asim Bilen
金额：
$ 65.18万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10579285
关键词：
16S ribosomal RNA sequencing Accounting Adverse event Aftercare Biological Markers Blood Blood specimen Butyrates Cancer Center Cancer Patient Clinical Complex Data Development Diagnosis Diet Diet Modification Disease Progression Disease remission Ethnic Origin Ethnic Population Freezing Future Genes Goals High-Throughput Nucleotide Sequencing Human Microbiome Immune checkpoint inhibitor Immunotherapy Individual Inflammation Integration Host Factors Life Style Malignant Neoplasms Measurement Mediating Neoplasm Metastasis Nephrectomy Outcome Pathogenesis Pathway interactions Patient Recruitments Patient Selection Patient risk Patients Pharmaceutical Preparations Phase Prevention strategy Production Progression-Free Survivals Questionnaires Race Recommendation Recurrent disease Renal Cell Carcinoma Renal carcinoma Reporting Research Resolution Risk Role Shotguns Specific qualifier value Supplementation T-Cell Activation Time Toxin Treatment outcome Treatment-related toxicity United States Universities Validation Volatile Fatty Acids Woman cancer immunotherapy cancer therapy demographics design experience gut microbes gut microbiome improved men metagenomic sequencing microbial microbiome prebiotics prevent prospective racial population response risk stratification sex standard of care stool sample treatment response whole genome

项目摘要

ABSTRACT In 2021, approximately 76,080 individuals in the United States will be diagnosed with kidney cancer, with renal cell carcinoma (RCC) accounting for >90% of all cases. Approximately 25% of patients with RCC present with metastasis at the time of initial diagnosis and up to 20-30% of patients develop recurrent disease after nephrectomy. Immunotherapy is a new standard-of-care option for the first-line treatment of intermediate-risk or poor-risk patients with advanced RCC. However, the immunotherapy outcomes are heterogeneous, with some patients achieving a complete remission, and others having no benefit at all. Therefore, it is important to identify modifiable factors and biomarkers that could help with patient selection and risk stratification, and to detect patients who will experience treatment-related adverse events and disease progression. Growing evidence supports that the gut microbiome contributes to cancer therapy toxicities and may modulate response to cancer therapy. Therefore, we propose to 1) identify and validate pre-treatment gut microbiome profiles, specific bacterial species, and bacterial functional pathways associated with circulating T-cell activation, cancer immunotherapy response, adverse events, and progression-free survival among patients with advanced RCC; 2) identify and validate cancer immunotherapy-associated changes in the gut microbiome profiles and bacterial functional pathways, and their association with circulating T-cell activation, cancer immunotherapy response, adverse events, and progression-free survival among patients with advanced RCC, 3) explore the role of bacterial metabolites and related biomarkers in cancer immunotherapy response, and 4) obtain preliminary data on the gut microbiome profiles and bacterial functional pathways and outcomes by sex and race. The study results will contribute considerably to our understanding of the role of the gut microbiome in cancer immunotherapy response, efficacy, and adverse events, and will be relevant not only for advanced RCC patients, but also for a larger group of cancer patients treated with cancer immunotherapy, which is considered to be most promising recent development in cancer therapy.

抽象的 2021 年，美国将有约 76,080 人被诊断患有肾癌，其中肾癌细胞癌（RCC）占所有病例的 90% 以上。大约 25% 的 RCC 患者存在以下症状：初次诊断时已发生转移，高达 20-30% 的患者在诊断后会出现复发性疾病肾切除术。免疫疗法是中危患者一线治疗的新标准护理选择或患有晚期肾细胞癌的低风险患者。然而，免疫治疗的结果是异质的，一些患者获得完全缓解，而另一些患者则完全没有获益。因此，重要的是确定可以帮助患者选择和风险分层的可修改因素和生物标志物，并检测将经历治疗相关不良事件和疾病进展的患者。生长有证据表明肠道微生物群会导致癌症治疗毒性并可能调节反应到癌症治疗。因此，我们建议 1) 识别和验证治疗前肠道微生物组概况，特定细菌种类以及与循环 T 细胞激活、癌症相关的细菌功能途径晚期肾细胞癌患者的免疫治疗反应、不良事件和无进展生存期； 2) 识别并验证癌症免疫治疗相关的肠道微生物组谱和细菌变化功能途径及其与循环 T 细胞激活、癌症免疫治疗反应的关联，不良事件和晚期 RCC 患者的无进展生存期，3) 探讨癌症免疫治疗反应中的细菌代谢物和相关生物标志物，4) 获得初步结果按性别和种族划分的肠道微生物组概况、细菌功能途径和结果的数据。这研究结果将极大地有助于我们了解肠道微生物组在癌症中的作用免疫治疗反应、疗效和不良事件，不仅与晚期肾细胞癌相关患者，也适用于接受癌症免疫疗法治疗的更大群体的癌症患者，这被认为是是癌症治疗领域最有前途的最新进展。