肿瘤免疫微环境结构与头颈部鳞状细胞癌复发风险相关联。
The tumor immune microenvironment architecture correlates with risk of recurrence in head and neck squamous cell carcinoma.
发表日期:2023 Aug 21
作者:
Donald T Weed, Serena Zilio, Christie McGee, Boutheina Marnissi, Zoukaa Sargi, Elizabeth Franzmann, Giovana Thomas, Jason Leibowitz, Elizabeth Nicolli, David Arnold, Silvio Bicciato, Paolo Serafini
来源:
CANCER RESEARCH
摘要:
新兴证据表明,肿瘤浸润性白细胞的频率、组成以及空间组织可能是肿瘤进展和治疗反应的重要决定因素。因此,绘制和分析肿瘤免疫微环境的精细结构可能为预测癌症预后提供见解。在本研究中,我们进行了一项探索性前瞻性临床研究,评估了头颈部鳞状细胞癌(HNSCC)的救助手术后肿瘤微环境内部结构是否能够预测复发。利用流式细胞术和索引共检测(CODEX)多参数成像测量了主要的免疫亚群。流式细胞术在测定肿瘤中PMN-MDSC和中性粒细胞数量时低估,而高估了肿瘤浸润淋巴细胞的频率。采用特制计算模型识别和分析离散的细胞邻域。在HNSCC中,由CD31highCD38high浆细胞组成的第三淋巴结结构的高频率与手术后复发减少相关。这些数据支持肿瘤免疫微环境的结构构架在肿瘤进展中起到重要作用,并表明类型1的第三淋巴结结构和长寿命的CD31highCD38high浆细胞与HNSCC的良好预后相关。
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. This data supports 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.