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:Spatial Distribution and Prognostic Value of T Cell Subtypes and Immune Biomarkers in p16-Negative HNSCC.
Spatial Distribution and Prognostic Value of T Cell Subtypes and Immune Biomarkers in p16-Negative HNSCC.
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头颈部鳞状细胞癌(HNSCC)患者发病负担和死亡率均较高。免疫治疗是一种新兴的有前景治疗选择,因此有必要深入了解其免疫生态位。
本研究分析84份HNSCC标本中不同T细胞亚型的空间分布和预后价值,以及与T细胞空间浸润相关的趋化因子和细胞因子水平。通过多色组织细胞计量术在单细胞水平定量辅助性T细胞(TH)、细胞毒性T淋巴细胞(CTL)及调节性T细胞(Treg)密度,并区分位于上皮肿瘤细胞巢和肿瘤间质中的T细胞。
此外,定量检测27种免疫相关因子。对p16阴性HNSCC患者进行生存分析发现,间质Treg密度较高是PFS和OS更佳的独立预后因素。
此外,CXCL10、IL-9和CCL4水平较高与T细胞数量显著增加相关,尤其是与肿瘤细胞直接接触的CTL;而在肿瘤间质中,VEGF表现出相反关联。
总之,Treg细胞浸润及特定细胞因子水平可作为p16阴性HNSCC的新型免疫生物标志物,用于预测生存及T细胞空间分布。
Patients with head and neck squamous cell carcinoma (HNSCC) suffer from severe morbidity and mortality. Immunotherapy represents a novel promising treatment option.
Therefore, a better understanding of the immune niche is needed.
This study focuses on the spatial distribution and prognostic value of different T cell subtypes in 84 HNSCC specimens as well as chemokine and cytokine levels associated with spatial T cell infiltration. Density of T helper (T H ), cytotoxic (CTL), and regulatory T cells (T reg ) was quantified by multicolor tissue cytometry on a single cell level in whole tissue sections, discriminating between T cells located in epithelial tumor cell nests or tumor stroma, respectively.
In addition, quantitative levels of 27 immune-related factors were assessed. Survival analysis of patients with p16-negative HNSCC revealed higher stromal T reg densities to be an independent prognostic factor for better progression-free and overall survival.
Furthermore, high levels of CXCL10, IL-9, and CCL4 were associated with significantly higher numbers of T cells, especially for CTL with direct contact to tumor cells, whereas for VEGF the opposite effect was observed in the tumor stroma.
In conclusion, T reg cell infiltration as well as distinct cytokine levels could serve as new immune biomarkers in p16-negative HNSCC to predict survival and the spatial distribution of T cells.
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