帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
英文原题:Identify metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 as potential prognostic markers and correlate with immune infiltrates in head and neck squamous cell carcinoma.
这些结果提示,HSCC 中发生了代谢重编程,并且与细胞应激和免疫反应相关,这可能有助于研究人员理解代谢重编程机制,并开发 HNSCC 的有效免疫治疗策略。
下咽鳞状细胞癌(HSCC)是头颈部鳞状细胞癌(HNSCC)的一种,预后较差。代谢重编程可通过快速适应细胞应激、调节免疫应答来改变肿瘤微环境(TME),但其在HSCC中的作用尚未报道。本研究使用nCounter代谢通路检测面板,分析HSCC组织和癌旁正常组织中的代谢重编程、细胞应激及其相互关系。与癌旁正常组织相比,HSCC组织中核苷酸合成和糖酵解通路显著上调,而氨基酸合成和脂肪酸氧化通路显著下调。代谢相关通路与细胞应激通路之间存在显著相关性。免疫细胞及TIL(肿瘤浸润淋巴细胞)富集分析显示,HSCC组织和癌旁正常组织的免疫应答存在差异。总生存分析表明,上调的CD276、LDHB、SLC3A2、EGFR、SLC7A5和HPRT1是HNSCC潜在的不良预后标志物;下调的EEA1、IDO1、NCOA2、REST、CCL19和ALDH2则是潜在的有利预后标志物。此外,代谢相关基因IDO1、ALDH2、NCOA2、SLC7A5、SLC3A2、LDHB和HPRT1与HNSCC中的免疫细胞浸润相关。结果提示,HSCC存在代谢重编程,且与细胞应激和免疫应答相关;这些发现有助于研究人员理解HNSCC代谢重编程机制并开发有效的免疫治疗策略。
Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of head and neck squamous cell carcinoma (HNSCC) with poor prognosis. Metabolic reprogramming may regulate the tumor microenvironment (TME) by adapting quickly to cellular stress and regulating immune response, but its role in HSCC has not been reported. We used the nCounter Metabolic Pathways Panel to investigate metabolic reprogramming, cellular stress, and their relationship in HSCC tissues and adjacent normal tissues. Metabolism-related pathways nucleotide synthesis and glycolysis pathways were significantly upregulated, while amino acid synthesis and fatty acid oxidation pathways were significantly downregulated in HSCC tissues compared to adjacent normal tissues. There is a significant correlation between metabolism-related pathways and cellular stress pathways. Enrichment of immune cell and tumor infiltrating lymphocyte (TIL) analysis showed changes in immune responses between HSCC tissues and adjacent normal tissues. Overall survival analysis showed that upregulated genes CD276, LDHB, SLC3A2, EGFR, SLC7A5, and HPRT1 are potential unfavorable prognostic markers in HNSCC, while downregulated genes EEA1, IDO1, NCOA2, REST, CCL19, and ALDH2 are potential favorable prognostic markers in HNSCC. Moreover, metabolism-related genes IDO1, ALDH2, NCOA2, SLC7A5, SLC3A2, LDHB, and HPRT1 are correlated with immune infiltrates in HNSCC. These results suggest that metabolic reprogramming occurs and correlates with cellular stress and immune response in HSCC, which may help researchers understand mechanisms of metabolic reprogramming and develop effective immunotherapeutic strategies in HNSCC.
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