鼻咽癌(NPC)是侵袭性恶性肿瘤之一,病死率高。髓源性抑制细胞(MDSCs)的增殖可能通过抑制T细胞的功能促进鼻咽癌的转移。同时,已知SPLUNC1抑制NPC细胞的恶性行为,而SPLUNC1在LPS修饰的NPC免疫微环境中的详细功能尚不清楚。为了评估SPLUNC1在鼻咽癌进展过程中对免疫微环境的影响,将NPC细胞暴露于LPS,然后与MDSCs共培养48h。进行RT-qPCR和Western印迹以分别评估SPLUNC1,CXCL-2和CXCR-2的mRNA和蛋白水平。IL-1β水平,IL-6,TNF-α,ELISA法检测PD-L1、Arg-1和iNOS。同时,流式细胞术检测CD33+的表达。NPC细胞中CXCL-2和CXCR-2的表达较高,与NP69细胞相比。相比之下,NPC细胞中的SPLUNC1水平远低于NP69细胞。SPLUNC1水平与CXCL-2和CXCR-2呈负相关。SPLUNC1的过表达逆转了LPS诱导的NPC细胞的炎症反应和增殖。此外,SPLUNC1上调可以逆转LPS诱导的肿瘤微环境中MDSCs的增殖。同时,SPLUNC1过表达可通过降低CXCL-2和CXCR-2蛋白和mRNA表达来调节CXCL-2/CXCR-2轴。SPLUNC1调节LPS诱导的鼻咽癌进展和MDSC增殖。因此,我们的研究可能为发现针对NPC的新策略提供理论基础。
Nasopharyngeal carcinoma (NPC) is one of the aggressive malignant tumors with high mortality, and the proliferation of myeloid-derived suppressor cells (MDSCs) could promote the metastasis of NPC through inhibiting the function of T cells. Meanwhile,
SPLUNC1 was known to inhibit the malignant behavior of NPC cells, while the detailed function of
SPLUNC1 in LPS-modified immune microenvironment of NPC remains unclear. To assess the impact of SPLUNC1 in immune microenvironment during the progression of NPC, NPC cells were exposed to LPS and then co-cultured with MDSCs for 48 h. RT-qPCR and western blot were performed to evaluate the mRNA and protein level of
SPLUNC1, CXCL-2 and CXCR-2, respectively. The level of IL-1β, IL-6, TNF-α, PD-L1, Arg-1 and iNOS were tested by ELISA. Meanwhile, the expression of CD33+ was tested by flow cytometry. The expression of CXCL-2 and CXCR-2 in NPC cells was higher, compared to that in NP69 cells. In contrast,
SPLUNC1 level in NPC cells was much lower than that in NP69 cells.
SPLUNC1 level was negatively correlated with CXCL-2 and CXCR-2. Overexpression of SPLUNC1 reversed LPS-induced inflammatory responses and proliferation in NPC cells. In addition, SPLUNC1 upregulation could reverse LPS-induced proliferation of MDSCs in tumor microenvironment. Meanwhile, SPLUNC1 overexpression could regulate CXCL-2/CXCR-2 axis through decreasing CXCL-2 and CXCR-2 protein and mRNA expression. SPLUNC1 regulates LPS-induced progression of nasopharyngeal carcinoma and proliferation of MDSCs. Thus, our study might provide a theoretical basis for discovering new strategies against NPC.