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

项目摘要/摘要 细胞外小泡作为细胞间信号转导和动脉粥样硬化的中介受到了广泛的关注。 癌症生物标志物的潜在来源。存在内吞来源的纳米级EV--外体。 在几乎所有类型的生物液中，都具有液体活组织检查和治疗应用的巨大潜力。 外切体运送含有免疫调节分子的货物，如受体、配体、抗原和/或 细胞因子。这种货物可以反映来源细胞，并对接受细胞产生影响。唾液 Exosome已被鉴定为具有临床相关信息的高度信息量的纳米囊泡。唾液 胞外体为肿瘤衍生生物标志物的穿梭提供了一条途径和机制 通过全身循环进入口腔。尽管有这样的临床潜力，唾液的作用 对于宿主和肿瘤的外切体的研究还很少。我们假设唾液外切体 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 肿瘤背景下唾液外切体的多肽谱系。鉴定唾液肽可以 激活或抑制淋巴细胞将为肿瘤的免疫控制提供新的见解，并可能揭示 免疫治疗的新靶点和新策略。此外，识别新的肿瘤来源或宿主来源 释放到唾液中的抗原不仅提供了对其潜在调节功能的洞察，而且还提供了 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.