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:The Tumor Immune Microenvironment Architecture Correlates with Risk of Recurrence in Head and Neck Squamous Cell Carcinoma.
The Tumor Immune Microenvironment Architecture Correlates with Risk of Recurrence in Head and Neck Squamous Cell Carcinoma.
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新出现的证据表明,不仅肿瘤浸润白细胞的频率和组成,而且其空间组织也可能是肿瘤进展和治疗反应的主要决定因素。因此,绘制和分析精细的肿瘤免疫结构可能为预测癌症预后提供见解。在此,我们进行了一项探索性、前瞻性临床研究,以评估肿瘤微环境中的结构是否能预测头颈部鳞状细胞癌(HNSCC)挽救性手术后的复发。使用流式细胞术和索引共检测(CODEX)多参数成像测量主要免疫亚群。流式细胞术低估了肿瘤中PMN-MDSC和中性粒细胞的数量,并高估了TIL(肿瘤浸润淋巴细胞)的频率。使用了一个专门的计算框架来识别和分析离散的细胞邻域。由CD31highCD38high浆细胞组成的高频率三级淋巴结构与HNSCC手术后复发减少相关。这些数据支持了肿瘤免疫微环境的结构架构在肿瘤进展中起重要作用的观点,并表明1型三级淋巴结构和长寿命CD31highCD38high浆细胞与HNSCC的良好预后相关。意义:对空间肿瘤免疫微环境进行成像并评估1型三级淋巴结构的存在,能够预测头颈部鳞状细胞癌患者手术后的复发。
UNLABELLED: Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy.
Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis.
Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods.
A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.
SIGNIFICANCE: Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.
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