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
口咽癌（OPSCC）中 TIL（肿瘤浸润淋巴细胞）的免疫检查点表达取决于 HPV 状态——单细胞 RNA 测序分析
英文原题：Immune checkpoint expression on tumor-infiltrating lymphocytes (TIL) is dependent on HPV status in oropharyngeal carcinoma (OPSCC) - A single-cell RNA sequencing analysis.
查看英文原题
Immune checkpoint expression on tumor-infiltrating lymphocytes (TIL) is dependent on HPV status in oropharyngeal carcinoma (OPSCC) - A single-cell RNA sequencing analysis.
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研究概要
本研究揭示了 OPSCC 中 ICMs 之间复杂的相互作用，强调有必要基于 HPV 状态和免疫特征采取个体化治疗策略。
中文摘要
材料与方法
对51例OPSCC开展RNA测序，并利用TCGA HNSCC数据集进行验证。根据HPV状态在R中开展无监督聚类和差异基因表达分析。此外，采用Seurat流程分析已发表的TIL（肿瘤浸润淋巴细胞）和外周免疫细胞（PBMC）单细胞RNA测序数据集（GSE139324），并按HPV状态分组。
结果
整体RNA测序显示，HPV阳性OPSCC中所有受检ICM均显著上调，且在TCGA队列中得到验证。无监督聚类显示，HPV阳性/阴性病例分别与ICM高/低表达病例强相关，提示ICM表达与HPV状态存在重叠。在单细胞RNA分析中，HPV阳性OPSCC的TIL中CD27、PD-1、OX-40和BTLA表达显著较高。相反，HPV阴性OPSCC的PBMC和TIL中VSIR升高，而PBMC中的LAG3表达降低。
结论
本研究揭示OPSCC中ICM之间复杂的相互作用，强调需根据HPV状态和免疫特征制定个体化治疗策略。已鉴定的ICM（包括PD-1、CD27和CTLA4）是值得进一步研究的候选靶点，可能增强基于HPV状态的OPSCC免疫治疗。
展开英文摘要原文
RESULTS
Our study identified a significant upregulation of all examined ICM in HPV-positive OPSCC through bulk RNA sequencing, validated by the TCGA cohort. Unsupervised clustering revealed a strong association between HPV-positive/-negative and high/low ICM expression cases respectively, indicating overlap between ICM and HPV status. In scRNA analysis, CD27, PD-1, OX-40, and BTLA were significantly more highly expressed on TILs of HPV-positive OPSCC. Conversely, VSIR was increased in PBMC and TILs of HPV-negative OPSCC, while LAG3 expression on PBMC was reduced in HPV-negative OPSCC.
CONCLUSION
Our study unveils the intricate interplay of ICMs in OPSCC, emphasizing the necessity for personalized therapeutic approaches based on HPV status and immune profiles. The identified ICMs, including PD1, CD27, and CTLA4, are promising candidates for further investigation and may enhance immunotherapeutic interventions in the HPV-dependent treatment strategies for OPSCC.
论文信息
- 作者
- von Witzleben A、Grages A、Thomas J、Ezić J、Brunner C、Schuler PJ、Kraus JM、Kestler HA
- 单位
- Department of Otorhinolaryngology and Head & Neck Surgery, Head and Neck Cancer Center of the Comprehensive Cancer Center Ulm, University Medical Center Ulm, Germany. Electronic address: adrian.vonwitzleben@uniklinik-ulm.de.Germany
- 文献类型
- 非美国政府资助研究
- 期刊
- Oral oncology2024 Dec
- 原文标识
- PubMed 39549431 · DOI 10.1016/j.oraloncology.2024.107107