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:Dickkopf-1 is an immune infiltration-related prognostic biomarker of head and neck squamous cell carcinoma.
Dickkopf-1 is an immune infiltration-related prognostic biomarker of head and neck squamous cell carcinoma.
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免疫治疗目前是头颈部鳞状细胞癌(HNSCC)最可行的治疗方法之一,其特征是免疫细胞高度浸润。Wnt信号抑制剂和免疫激活介质Dickkopf-1(DKK1)与肿瘤生长、肿瘤微环境以及由此导致的疾病预后密切相关。
然而,DKK1表达、HNSCC预后与TIL(肿瘤浸润淋巴细胞)之间的关系仍不清楚。为了更好地理解这些关联,我们检测了DKK1表达在不同肿瘤和正常组织中的差异。
在本研究中,我们探讨了DKK1 mRNA表达与临床结局之间的关联。接下来,我们评估了DKK1表达与肿瘤免疫细胞浸润之间的联系。
此外,我们采用免疫组织化学方法,评估了15份健康头颈部组织样本中DKK1的表达,以及27份HNSCC样本中CD3、CD4和DKK1的表达。
我们还探索了肿瘤发生过程中DKK1的异常表达。DKK1在HNSCC组织中的表达显著高于健康组织,并被证明与HNSCC的肿瘤分期、分级、淋巴结转移、组织学类型及不良临床预后相关。HNSCC组织中DKK1表达与CD3+(P < 0.0001)和CD4+(P < 0.0001)免疫细胞浸润呈负相关,而免疫细胞中DKK1表达与HNSCC预后呈负相关。这些发现为DKK1在HNSCC免疫治疗中的功能提供了生物信息学视角,并为DKK1靶向HNSCC治疗的临床研究提供了依据。DKK1是提高HNSCC免疫治疗疗效的核心靶点。
Immunotherapy is currently one of the most viable therapies for head and neck squamous cell carcinoma (HNSCC), characterized by high immune cell infiltration. The Wnt-signaling inhibitor and immune activation mediator, Dickkopf-1 (DKK1), has a strong correlation with tumor growth, tumor microenvironment, and, consequently, disease prognosis.
Nevertheless, it is still unclear how DKK1 expression, HNSCC prognosis, and tumor-infiltrating lymphocytes are related. To better understand these associations, we examined how DKK1 expression varies across different tumor and normal tissues. In our study, we investigated the association between DKK1 mRNA expression and clinical outcomes. Next, we assessed the link between DKK1 expression and tumor immune cell infiltration.
Additionally, using immunohistochemistry, we evaluated the expression of DKK1 in 15 healthy head and neck tissue samples, and the expression of CD3, CD4, and DKK1 in 27 HNSCC samples.
We also explored aberrant DKK1 expression during tumorigenesis. DKK1 expression was remarkably higher in HNSCC tissues than in healthy tissues, and was shown to be associated with tumor stage, grade, lymph node metastasis, histology, and a dismal clinical prognosis in HNSCC. DKK1 expression in HNSCC tissues was inversely correlated with CD3+ (P < 0. 0001) and CD4+ (P < 0. 0001) immune cell infiltration, while that in immune cells was inversely associated with HNSCC prognosis.
These findings offer a bioinformatics perspective on the function of DKK1 in HNSCC immunotherapy and provide justification for clinical research on DKK1-targeted HNSCC treatments. DKK1 is a central target for improving the efficacy of HNSCC immunotherapy.
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