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:High-Sensitivity PD-L1 Staining Using Clone 73-10 Antibody and Spatial Transcriptomics for Precise Expression Analysis in Non-Tumorous, Intraepithelial Neoplasia, and Squamous Cell Carcinoma of Head and Neck.
High-Sensitivity PD-L1 Staining Using Clone 73-10 Antibody and Spatial Transcriptomics for Precise Expression Analysis in Non-Tumorous, Intraepithelial Neoplasia, and Squamous Cell Carcinoma of Head and Neck.
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克隆 73-10 是识别 PD-L1 表达、适合接受 ICI 治疗患者的相对合适候选标志物。它在检测 HNSCC 中的 PD-L1(CD274)方面表现出高敏感性,并提供了免疫学和预后方面的见解。
尽管靶向PD-1/PD-L1轴的免疫检查点抑制剂(ICIs)改善了头颈部鳞状细胞癌(HNSCC)的预后,但基于免疫组织化学(IHC)的纳入标准仅针对PD-1。我们旨在使用高灵敏度克隆73-10和空间转录组学(ST)分析来评估PD-L1(CD274)的表达,以阐明PD-L1在HNSCC中的作用,从而可能扩大合格患者的范围。
对94例HNSCC临床样本及配对的邻近鳞状上皮内瘤变(SIN)和正常口腔黏膜(NOM)样本进行了73-10、CD3、CD4和CD8的免疫组化染色。73-10阳性以肿瘤细胞评分≥1%进行评估,并将结果与临床病理特征(包括CD4+和CD8+TIL(肿瘤浸润淋巴细胞)(TILs))及临床结局进行分析。此外,对6对配对的HNSCC、SIN和NOM样本进行了ST和PD-L1相关通路分析。
73-10检测的PD-L1阳性在HNSCC中较高(79%),而SIN为10%,NOM为3%。73-10+与高CD4+TILs相关,并且是HNSCC的OS、DSS和PFS的独立预后因素(均p<0.05)。ST分析显示,CD274的上调分布与73-10阳性相关。通路分析显示,与SIN和NOM相比,HNSCC中CD274和CD4显著上调,HIF-1α和IFN-γ是HNSCC中PD-L1表达的关键调节因子。
While immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have improved outcomes in head and neck squamous cell carcinoma (HNSCC), eligibility criteria based on immunohistochemistry (IHC) target PD-1 solely. We aimed to evaluate the PD-L1 (CD274) expression using highly sensitive clone 73 - 10 and spatial transcriptomics (ST) analysis to elucidate the role of PD-L1 in HNSCC and thus potentially expand the pool of eligible patients.
Immunohistochemical staining of 73 - 10, CD3, CD4, and CD8 were performed in 94 HNSCC clinical samples along with paired adjacent squamous intraepithelial neoplasm (SIN) and normal oral mucosa (NOM) samples. The 73 - 10 positivity was evaluated using a tumor cell score ≥ 1%, and the results were analyzed against clinicopathological features including CD4 + and CD8 + tumor-infiltrating lymphocytes (TILs), and clinical outcomes. Furthermore, ST and PD-L1 related pathway analysis was performed in 6 paired HNSCC, SIN and NOM samples.
The 73 - 10 detected-PD-L1 positivity was high in HNSCC (79%) compared to SIN (10%) and NOM (3%). 73 - 10 + correlated with high CD4 + TILs, as well as the independent prognostic factor of OS, DSS, and PFS of HNSCC (all p < 0.05). ST analysis revealed that the upregulated distribution of CD274 correlated with 73 - 10 positivity. Pathway analysis revealed a significant upregulation of CD274 and CD4 in HNSCC compared to SIN and NOM, and HIF-1α and IFN-γ as key regulators of PD-L1 expression in HNSCC.
Clone 73 - 10 is a relatively suitable candidate for identifying patients with PD-L1 expression eligible for ICI therapy. It demonstrates high sensitivity in detecting PD-L1 (CD274) in HNSCC, offering immunological and prognostic insights.
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