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:Expression of PD-L1 and CD4+ tumor-infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma.
Expression of PD-L1 and CD4+ tumor-infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma.
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免疫检查点阻断的临床疗效近期已在多种癌症类型中得到证实。本研究旨在表征头颈部鳞状细胞癌(HNSCC)中TIL(肿瘤浸润淋巴细胞)(TILs)和程序性死亡配体1(PD-L1)的表达谱。
本研究共纳入63例HNSCC患者。通过免疫组织化学检测CD3+和CD4+TILs及PD-L1的表达。通过逆转录定量PCR分析评估PD-L1 mRNA水平。
同时评估TILs和PD-L1与患者临床病理特征的相关性。CD3+和CD4+TILs在100%的样本中均被检出。CD3+是TILs的主要亚群。当肿瘤细胞评分≥1被视为阳性时,PD-L1在61例患者中的53例(86%)中表达;当肿瘤细胞评分>5被视为阳性时,PD-L1在28例患者(45.2%)中表达。PD-L1 mRNA水平被确定与PD-L1蛋白表达显著相关。生存分析表明,高CD4+TILs与改善的总生存期(OS)和无病生存期(DFS)相关,此外,高PD-L1表达与不良OS和DFS的相关性具有统计学意义。多因素分析确定CD4+TILs和PD-L1为HNSCC的预后标志物。
本研究结果表明,HNSCC中CD4+TILs增加可能与改善的预后相关,而PD-L1高表达可能提示不良OS和DFS;因此,这些因素可作为免疫检查点治疗反应的预测指标。
The clinical efficacy of immune checkpoint blockade has been recently demonstrated in a variety of cancer types. The aim of the present study was to characterize the expression profile of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) in head and neck squamous carcinoma (HNSCC). A total of 63 patients with HNSCC were enrolled in the present study. CD3 + and CD4 + TILs and the expression of PD-L1 were detected by immunohistochemistry. PD-L1 mRNA levels were evaluated by reverse transcription-quantitative PCR analysis. The association of TILs and PD-L1 with patient clinicopathological characteristics was also assessed. CD3 + and CD4 + TILs were detected in 100% of the samples. CD3 + was the predominant subset of TILs. PD-L1 was expressed in 53 of 61 (86%) patients when a score of ≥1 on tumor cells was considered positive and in 28 patients (45.
2%) when a score of >5 on tumor cells was considered positive. PD-L1 mRNA levels were determined to be significantly correlated with PD-L1 protein expression. Survival analysis demonstrated that high CD4 + TILs were associated with improved overall survival (OS) and disease-free survival (DFS), and furthermore, the association of high PD-L1 expression with unfavorable OS and DFS was statistically significant.
Multivariate analysis identified CD4 + TILs and PD-L1 as prognostic markers for HNSCC. The results of the present study suggested that increased CD4 + TILs in HNSCC may be associated with improved outcomes, while high expression of PD-L1 may indicate unfavorable OS and DFS; thus, these factors may serve as predictors of the response to immune checkpoint therapy.
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