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。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CCR5 as a prognostic biomarker correlated with immune infiltrates in head and neck squamous cell carcinoma by bioinformatic study.
CCR5 as a prognostic biomarker correlated with immune infiltrates in head and neck squamous cell carcinoma by bioinformatic study.
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CCR5 的高表达在 HNSC 患者中具有重要的预后作用,并可能作为与免疫浸润相关的预后生物标志物,未来仍需进一步研究以探索针对 HNSC 患者的治疗靶点。
C-C趋化因子受体5(CCR5)最近被认为是多种恶性肿瘤的潜在治疗靶点。然而,CCR5与头颈部鳞状细胞癌(HNSC)患者预后及TIL(肿瘤浸润淋巴细胞)(TILs)的关联尚不清楚。
在本实验中,采用肿瘤免疫估计资源分析(TIMER)、基因表达谱交互分析(GEPIA)、UALCAN和Kaplan-Meier绘图分析等方法,综合评估CCR5在人类多种恶性肿瘤中的表达及HNSC患者的临床预后。随后,我们利用TIMER数据库和TISIDB平台研究CCR5表达水平与HNSC肿瘤微环境中免疫细胞浸润的相关性。此外,使用TISIDB平台进行免疫调节和趋化因子谱分析,以分析HNSC患者中CCR5表达水平与免疫调节的相关性。
我们发现HNSC肿瘤组织中CCR5的表达显著高于正常组织。在HNSC中,CCR5表达水平高的患者总体生存期(OS,HR = 0.59,p = 0.00015)和无复发生存期(RFS,HR = 3.27,p = 0.00098)较差。CCR5表达上调与免疫调节因子、趋化因子以及CD4+ T细胞、中性粒细胞、巨噬细胞和髓系树突状细胞的浸润水平密切相关。此外,CCR5上调与HNSC免疫细胞亚群中的不同免疫标志物显著相关。
C-C chemokine receptor 5 (CCR5) has recently been recognized as an underlying therapeutic target for various malignancies. However, the association of CCR5 with prognosis in the head and neck squamous cell carcinoma (HNSC) patients and tumor-infiltrating lymphocytes (TILs) is unclear.
In the current experiment, methods such as the Tumor Immune Estimation Resource Analysis (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier plotter Analysis were used to comprehensively evaluate the expression of CCR5 in human various malignancies and the clinical prognosis in HNSC patients. Subsequently, we used the TIMER database and the TISIDB platform to investigate the correlation between CCR5 expression levels and immune cell infiltration in the HNSC tumor microenvironment. Furthermore, immunomodulatory and chemokine profiling were performed using the TISIDB platform to analyse the correlation between CCR5 expression levels and immunomodulation in HNSC patients.
We found that CCR5 expression in HNSC tumor tissues was significantly upregulated than in normal tissues. In HNSC, patients with high CCR5 expression levels had worse overall survival (OS, HR = 0.59, p = 0.00015) and worse recurrence-free survival (RFS, HR = 3.27, p = 0.00098). Upregulation of CCR5 expression is closely associated with immunomodulators, chemokines, and infiltrating levels of CD4+ T cells, neutrophils, macrophages, and myeloid dendritic cells. Furthermore, upregulated CCR5 was significantly associated with different immune markers in the immune cell subsets of HNSC.
High expression of CCR5 plays an important prognostic role in HNSC patients and may serve as a prognostic biomarker correlated with immune infiltration, and further studies are still needed to investigate therapeutic targeting HNSC patients in the future.
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