PRCR协助转移起始细胞免疫逃逸促进鼻咽癌转移的机制研究

远处转移占鼻咽癌总死亡原因的70%，而转移起始细胞被认为是肿瘤转移的根源。我们前期工作发现：①在发生远处转移患者的鼻咽癌组织中，CD45-CD44-/lowMERx+肿瘤细胞亚群比例明显升高，其高表达干性相关基因且具有体内转移瘤形成能力；②该肿瘤细胞亚群高表达免疫抑制分子PRCR，能通过分泌IL-10抑制T细胞杀伤能力，且PRCR+肿瘤细胞富集在血管附近。因此我们提出科学假说：CD45-CD44-/lowMERx+细胞亚群高表达PRCR，能够被微环境细胞分泌的配体激活后刺激IL-10分泌，从而抑制免疫实现鼻咽癌转移。本课题拟继续开展：①明确CD45-CD44-/lowMERx+细胞亚群具有转移起始细胞特征且能预测鼻咽癌患者转移风险；②揭示肿瘤微环境细胞如何诱导PRCR阳性转移起始细胞分泌IL-10实现免疫逃逸促进鼻咽癌转移的分子机制。通过本项目的实施，为鼻咽癌抗转移治疗提供分子指标和靶点。

Distant metastasis is the main reason of treatment failure in nasopharyngeal carcinoma (NPC) patients, accounting for 70% cases. Metastasis initiating cells are considered as the source of tumor metastasis. Our previous study found that:①the proportion of CD45-CD44-/lowMERx+ tumor cell subpopulation was significantly increased in the primary tumor tissues of NPC patients diagnosed with distant metastasis，this subpopulation expressed with high levels of stemness markers and could form metastatic tumors in vivo;②PRCR was found to be upregulated in this tumor cell subpopulation which can inhibit the killing ability of T cells by secreting IL-10, and PRCR+ tumor cells are enriched near blood vessels. Therefore, the scientific hypothesis proposed in this project is: with high expression of PRCR in CD45-CD44-/lowMERx+ cell subsets, it can secrete IL-10 after activation by ligands that secreted by microenvironment cells, thus achieve immunity inhibition and metastasis of nasopharyngeal carcinoma. Based on the above foundation, we’ll conducted studies as follows:①clarify that the CD45-CD44-/lowMERx+ subset has the characteristics of metastasis initiating cells and can predict the risk of metastasis in patients with nasopharyngeal carcinoma; ②reveal the molecular mechanism of how tumor microenvironment cells induce PRCR positive metastasis initiating cells to secrete IL-10, to achieve immune escape and metastasis of nasopharyngeal carcinoma. Through the implementation of this project, it would provide molecular indicators and novel target for anti-metastatic therapy.