Defining a novel function for salivary exosomes in modulating host immunity against cancer

项目总结/摘要 细胞外囊泡（EV）作为细胞间信号传导的介质和作为细胞内信号转导的载体已经获得了相当大的关注。 癌症生物标志物的潜在来源。外泌体是内吞来源的纳米级EV， 在几乎所有类型的生物流体中，具有液体活检和治疗应用的巨大潜力。 外泌体递送含有免疫调节分子如受体、配体、抗原和/或其组合的货物。 细胞因子这种货物可以反映起源细胞，并对受体细胞产生影响。唾液 外来体已被鉴定为具有临床相关信息的高度信息化的纳米囊泡。唾液 外泌体为肿瘤生物标志物的穿梭提供了途径和机制 通过全身循环进入口腔。尽管有这样的临床潜力，唾液酸的作用， 外泌体对宿主和肿瘤的作用还没有得到充分的研究。我们假设唾液外泌体 通过粘膜免疫系统发挥免疫调节作用。在这个项目中，我们将确定独特的 在肿瘤背景下装载唾液外泌体的肽库。确定唾液肽， 激活或抑制淋巴细胞将为肿瘤的免疫控制提供新的见解， 免疫治疗的新靶点和策略。此外，鉴定新的肿瘤或宿主来源的 释放到唾液中的抗原不仅可以深入了解其潜在的调节功能， 诊断价值

Project Summary/Abstract Extracellular vesicles (EVs) have gained considerable attention as mediators of intercellular signaling and as potential sources of cancer biomarkers. Exosomes, which are nanoscale EVs of endocytic origin, are present in nearly all types of biofluids, carrying a tremendous potential for liquid biopsy and therapeutic applications. Exosomes deliver cargo containing immunoregulatory molecules such as receptors, ligands, antigens, and/or cytokines. This cargo can be reflective of the cell of origin and have effects on recipient cells. Salivary exosomes have been identified as highly informative nanovesicles with clinically relevant information. Salivary exosomes have brought forth a pathway and mechanism in which tumor-derived biomarkers can be shuttled through the systemic circulating into the oral cavity. Despite such clinical potential, the role of salivary exosomes for the host and tumor has been greatly understudied. We hypothesize that salivary exosomes have immunomodulatory effects through mucosal immune system. In this project, we will determine the unique peptide repertoire loading salivary exosomes in the setting of tumor. Identifying the salivary peptides that can activate or inhibit lymphocytes will provide new insights into the immune control of tumor and may uncover novel targets and strategies for immunotherapeutics. Moreover, identifying novel tumor- or host-derived antigens released into saliva will provide not only insight into its potential regulatory function but also the diagnostic value.