Differentiation and function of transitional monocytes in cancer metastasis to the lung

移行单核细胞在癌症肺转移中的分化和功能

• 批准号: 10748569
• 负责人: Minhee (Emily) Park
• 金额: $ 4.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-28 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748569
• 关键词: Activated Natural Killer Cell; Affect; Algorithms; Automobile Driving; Bone Marrow; CSF1 gene; Cause of Death; Cells; Chimera organism; Complement; Data; Dendritic Cells; Disseminated Malignant Neoplasm; Distal; Engineering; Family; Floods; Flow Cytometry; Future; Goals; Growth; Hematologic Neoplasms; Hour; Immune; Immune response; Immunity; In Vitro; Infiltration; Injections; Knockout Mice; Literature; Lung; Macrophage; Malignant Neoplasms; Mediating; Melanoma Cell; Membrane Proteins; Metastatic Neoplasm to the Lung; Modeling; Molecular; Mus; Natural Killer Cells; Neoplasm Circulating Cells; Neoplasm Metastasis; Organ; Pathway interactions; Patients; Pattern; Phagocytes; Phagocytosis; Phase; Phenotype; Play; Primary Neoplasm; Process; Receptor Signaling; Reporting; Role; SLAM protein; Signal Induction; Signal Pathway; Signal Transduction; Site; Solid; Surface; System; Techniques; Testing; Time; Tissues; Transgenic Mice; Up-Regulation; assault; cancer cell; cell killing; cell type; effective therapy; epigenomic profiling; in vivo; insight; monocyte; multiple omics; neoplastic cell; novel therapeutic intervention; novel therapeutics; permissiveness; prevent; protein expression; proteomic signature; recruit; residence; response; transcriptomic profiling; tumor; tumor microenvironment

Project Summary/Abstract Cancer metastasis occurs when cancer cells spread to distal organs from their site of origin, and it is the leading cause of death in patients with solid cancers. When cancer spreads to the lung, various types of innate immune cells either help or inhibit this colonization process. Monocytes are one of the earliest cell types to flood the lung during the beginning of metastasis. These monocytes eventually become tumor-supporting metastasis-associated macrophages (MAMs), and many studies in the field have reported that monocytes and MAMs actively aid metastatic cancer to infiltrate the lung and take residence there. My project aims to understand how monocytes differentiate into MAMs; in particular, what signals and factors are critical for this transition to occur in the lung. Furthermore, from my preliminary data, I have identified a time window during which monocytes have undergone clear phenotypic changes but have not yet fully developed into MAMs. Interestingly, this transition period also coincides with the anti-tumor activity of other immune cell types, such as natural killer (NK) cells. Therefore, I aim to study the interactions between pro-tumoral monocytes and anti- tumoral NK cells during the first several hours of cancer metastasis to the lung. By understanding how the mechanisms that underlie these interactions help to increase the odds of metastatic establishment in the lung, I will be able to contribute valuable insights towards novel therapeutic efforts to prevent metastasis.

项目摘要/摘要 当癌细胞从起源地扩散到远端器官时，就会发生癌症转移，它是 实体癌患者的主要死因。当癌症扩散到肺部时，各种先天的 免疫细胞要么帮助，要么抑制这一殖民过程。单核细胞是最早的 转移开始时肺脏充血。这些单核细胞最终成为支持肿瘤的细胞 转移相关巨噬细胞(MAM)，以及该领域的许多研究报告，单核细胞和 MAMs积极帮助转移性癌症渗入肺部并在那里定居。我的项目旨在 了解单核细胞如何分化为巨噬细胞集落刺激因子；尤其是，哪些信号和因素对此至关重要 过渡发生在肺部。此外，根据我的初步数据，我已经确定了一个时间窗口 哪些单核细胞已经发生了明显的表型变化，但尚未完全发育为巨噬细胞集落刺激因子。 有趣的是，这一过渡期也与其他免疫细胞类型的抗肿瘤活性相吻合，如 作为自然杀伤(NK)细胞。因此，我旨在研究促肿瘤单核细胞与抗肿瘤单核细胞之间的相互作用。 肿瘤中的NK细胞在肿瘤转移到肺部的头几个小时。通过理解如何将 这些相互作用的基础机制有助于增加肺转移建立的几率，即 将能够为预防转移的新的治疗努力贡献有价值的见解。