In vivo Monitoring of Neutrophil Function in Patients after Stem Cell Transplant

干细胞移植后患者中性粒细胞功能的体内监测

基本信息

批准号：
10679553
负责人：
Daniel Irimia
金额：
$ 81.7万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-13 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10679553
关键词：
Acceleration Address Antifungal Agents Azoles Biological Markers CSF3 gene Candida Candida albicans Candida auris Candidiasis Cells Communication Diagnosis Early Diagnosis Effectiveness Engineering Enrollment Functional disorder Fungal Drug Resistance Future Goals Growth Hematologic Neoplasms Hematopoietic Stem Cell Transplantation Hospitalization Human Hyphae Image Imaging Techniques Immune response In Vitro Individual Infection Injury Knowledge Label Leukocytes Life Malignant Neoplasms Measurement Measures Microscopic Molecular Monitor Morbidity - disease rate Mycoses Outcome Patients Performance Phagocytosis Population Predisposition Procedures Prophylactic treatment Recovery Research Resistance Risk Risk Estimate Risk Factors Risk Reduction Role Site Stem cell transplant Techniques Therapeutic Time Transplant Recipients Transplantation accurate diagnosis candidemia chemokine cytokine design first responder functional restoration fungus high risk human imaging improved improved outcome in vivo in vivo monitoring infection risk leukemia mortality neutrophil novel imaging technology patient stratification post-transplant restoration tissue injury tool

Acceleration Address Antifungal Agents Azoles Biological Markers CSF3 gene Candida Candida albicans Candida auris Candidiasis Cells Communication Diagnosis Early Diagnosis Effectiveness Engineering Enrollment Functional disorder Fungal Drug Resistance Future Goals Growth Hematologic Neoplasms Hematopoietic Stem Cell Transplantation Hospitalization Human Hyphae Image Imaging Techniques Immune response In Vitro Individual Infection Injury Knowledge Label Leukocytes Life Malignant Neoplasms Measurement Measures Microscopic Molecular Monitor Morbidity - disease rate Mycoses Outcome Patients Performance Phagocytosis Population Predisposition Procedures Prophylactic treatment Recovery Research Resistance Risk Risk Estimate Risk Factors Risk Reduction Role Site Stem cell transplant Techniques Therapeutic Time Transplant Recipients Transplantation accurate diagnosis candidemia chemokine cytokine design first responder functional restoration fungus high risk human imaging improved improved outcome in vivo in vivo monitoring infection risk leukemia mortality neutrophil novel imaging technology patient stratification post-transplant restoration tissue injury tool

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项目摘要

Hematopoietic stem cell transplant (HSCT), an essential procedure in the treatment of patients with hematological malignancies, also temporarily increases the risk for infections with invasive fungi. The recovery in the neutrophil number after HSCT is commonly regarded as a key metric for the restoration of antifungal defenses. However, the metric is imprecise, and there is an urgent need for new biomarkers to help identify the patients at risk. In the absence of new tools, the management of invasive fungal infections remains remarkably challenging. The long-term goal of this research is to engineer new tools and validate new metrics estimating the risk for invasive fungal infections in HSCT patients. Achieving this goal requires a focus on neutrophil swarming function, which is critical in effective antifungal immune responses. Swarming is distinct from phagocytosis in that it involves neutrophil-neutrophil communication that helps coordinate the activities of multiple cells toward blocking the growth of invasive fungi. The focus on neutrophil swarming is justified by preliminary results showing that in HSCT patients, even when the neutrophil count recovered at 4 weeks after transplant, a neutrophil swarming deficiency is still present and is substantial. Knowledge about how neutrophil swarming deficiency is resolved over time after HSCT is currently lacking. To address this knowledge gap and evaluate the utility of new biomarkers we will pursue the following specific aims: 1) Determine neutrophil swarming parameters that are distinct in healthy and HSCT patients. 2) Determine what cytokines help restore the swarming activity of neutrophils from HSCT patients and 3) Design new imaging techniques for label-free tracking of human neutrophils responding to microscopic tissue injuries in vivo. If successful, the proposed research could have a major impact on the lives of HSCT patients by improving the monitoring of their recovery and by identifying potential strategies for accelerating the recovery of their neutrophil functions and improving their protection against fungal infections.

造血干细胞移植（HSCT），这是治疗患者的重要程序血液学恶性肿瘤也暂时增加了侵入性真菌感染的风险。恢复在HSCT之后的中性粒细胞中，通常被认为是恢复抗真菌的关键指标防御。但是，该指标是不精确的，迫切需要新的生物标志物来帮助识别有风险的患者。在没有新工具的情况下，侵入性真菌感染的管理仍然非常明显具有挑战性的。这项研究的长期目标是设计新工具并验证新的指标估计 HSCT患者侵入性真菌感染的风险。实现这一目标需要专注于中性粒细胞蜂群功能，这对于有效的抗真菌免疫反应至关重要。蜂群与吞噬作用是因为它涉及中性粒细胞中性粒细胞的交流，有助于协调多个细胞旨在阻断侵入性真菌的生长。对中性粒细胞群的关注是合理的初步结果表明，在HSCT患者中，即使中性粒细胞计数在后4周回收移植，中性粒细胞蜂群缺乏症仍然存在，而且很重要。关于中性粒细胞的知识 HSCT目前缺乏后，随着时间的推移解决了蜂群缺陷。解决此知识差距和评估新生物标志物的效用，我们将追求以下特定目的：1）确定中性粒细胞在健康和HSCT患者中与众不同的蜂群参数。 2）确定哪些细胞因子有助于恢复来自HSCT患者的中性粒细胞的蜂群活性和3）设计无标签的新成像技术跟踪人类中性粒细胞对体内微观组织损伤的反应。如果成功，提议研究可能会通过改善恢复监测来对HSCT患者的生活产生重大影响通过确定加速其中性粒细胞功能恢复并改善的潜在策略他们的保护防止真菌感染。