Nagl S, Haas M, Lahmer G, Büttner-Herold M, Grabenbauer G G, Fietkau R, Distel L V
Department of Radiation Oncology, University Hospitals and Friedrich-Alexander-University of Erlangen-Nürnberg , Erlangen, Germany.
Department of Radiology, Charité , Campus Benjamin Franklin , Berlin, Germany.
Oncoimmunology. 2016 Jan 13;5(5):e1127494. doi: 10.1080/2162402X.2015.1127494. eCollection 2016 May.
Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirty-eight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3(+) cells with either CD8(+), CD1a(+) or CD20(+) cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a(+) and CD20(+) cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20(+) cells had a non-random distribution pattern. A non-random distance between CD20(+) and FoxP3(+) cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3(+) cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a(+) cells are non-functional as are the intraepithelial CD20(+) cells, while stromal CD20(+) cells and FoxP3(+) cells are functional cells.
除了其单纯的存在之外，炎症细胞的分布模式特别引人关注。我们的假设是，随机分布可能是由于缺乏相互作用而无功能的明确指标。在此，我们评估了肛管鳞状细胞癌中炎症细胞之间细胞间距的意义以及与生存数据的可能关联。使用组织微阵列、双重染色免疫组织化学、全切片扫描和图像分析软件对38例肛管癌患者进行了研究。治疗包括同步放化疗。对基质和上皮内肿瘤浸润性炎症细胞（TIC）的数量以及细胞之间的距离进行了量化。对FoxP3(+)细胞与CD8(+)、CD1a(+)或CD20(+)细胞进行了双重染色。将测量的细胞间距与计算机模拟的细胞间距进行比较后，得出免疫细胞呈非随机分布因而具有功能的假设。上皮内CD1a(+)和CD20(+)细胞呈随机分布，因此被视为无功能。相反，基质CD20(+)细胞具有非随机分布模式。CD20(+)与FoxP3(+)细胞之间的非随机距离与明显不利的预后相关。测量的FoxP3(+)细胞之间的距离明显短于预期，表明调节性T细胞（Treg）处于功能活跃状态。分析TIC之间的细胞间距有可能区分受抑制的无功能炎症细胞和功能活跃的炎症细胞。我们得出结论，在这个肿瘤模型中，大多数CD1a(+)细胞和上皮内CD20(+)细胞一样无功能，而基质CD20(+)细胞和FoxP3(+)细胞是功能细胞。
