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:CMTM6 status predicts survival in head and neck squamous cell carcinoma and correlates with PD-L1 expression.
CMTM6 status predicts survival in head and neck squamous cell carcinoma and correlates with PD-L1 expression.
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我们回顾性分析了129例未经治疗的头颈部鳞状细胞癌(HNSCC),检测程序性死亡配体1(PD-L1)、CKLF样MARVEL跨膜结构域蛋白6(CMTM6)、肿瘤浸润白细胞(TIL)和肿瘤相关巨噬细胞(TAM)的表达,并评估这些标志物与人乳头瘤病毒(HPV)状态及总生存期(OS)的关系。约70%的HNSCC中可检测到PD-L1及CMTM6(综合阳性评分[CPS] 1和5)。HPV状态对标志物表达无显著影响。多数PD-L1阳性病例同时表达CMTM6,且染色模式相似。尽管PD-L1和CMTM6 mRNA表达水平分别与PD-L1和CMTM6蛋白状态相关,但PD-L1 mRNA与CMTM6 mRNA表达之间未见显著相关性。
表达PD-L1(p<0.0001)和/或CMTM6(p<0.05)的肿瘤与最佳OS相关。TIL密度较高(p<0.01)、CD8+ T细胞密度较高(p<0.001)及CD68/CD163比值>1均具有预后意义。多变量Cox回归显示,除HPV状态和PD-L1、CD8+ T细胞外,CMTM6也是独立预后因素。PD-L1和CMTM6与TIL及CD8+细胞相关,但与HPV无关。研究结果确定CMTM6是TIL、CD8+ T细胞和PD-L1相互作用网络中的重要伙伴,并参与介导抗癌疗效。评估CMTM6有助于预后预测,也可能作为免疫治疗选择的可靠生物标志物。
We retrospectively analyzed 129 treatment-na ve head and neck squamous cell carcinomas (HNSCCs) for the expression of programmed death ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), tumor-infiltrating leukocytes (TILs), and tumor-associated macrophages (TAMs).
We evaluated the relationships among these markers, human papilloma virus (HPV) status, and overall survival (OS). PD-L1 and CMTM6 (combined positive score (CPS) 1 and 5) were detected in ~ 70% of HNSCCs. HPV status had insignificant effects on marker expression. Most PD-L1-positive cases showed concomitant CMTM6 expression with comparable staining patterns.
While PD-L1 and CMTM6 mRNA expression levels correlated with PD-L1 and CMTM6 protein status, no significant correlation was observed for PD-L1 and CMTM6 mRNA expression. Tumors expressing PD-L1 (p < 0. 0001) and/or CMTM6 (p < 0. 05) were associated with the best OS. A high density of TILs (p < 0. 01), CD8 + T cells (p < 0. 001), and CD68/CD163 ratio > 1 were prognostically relevant.
In addition to HPV status, PD-L1 and CD8 + T cells, CMTM6 was identified as an independent prognostic factor using a multivariate Cox regression analysis. PD-L1 and CMTM6 correlated with TILs and CD8 + cells but not with HPV.
Our results identified CMTM6 as an important interaction partner in the crosstalk between TILs, CD8 + T cells, and PD-L1, which mediates anticancer efficacy. Assessments of CMTM6 may be helpful for prognostic prediction, and it may serve as a reliable biomarker for immunotherapy selection.
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