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FoxP3+和CD8+肿瘤浸润性T细胞的空间分布反映了它们的功能活性。

Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity.

作者信息

Posselt Rebecca, Erlenbach-Wünsch Katharina, Haas Matthias, Jeßberger Jonas, Büttner-Herold Maike, Haderlein Marlen, Hecht Markus, Hartmann Arndt, Fietkau Rainer, Distel Luitpold V

机构信息

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

出版信息

Oncotarget. 2016 Sep 13;7(37):60383-60394. doi: 10.18632/oncotarget.11039.

DOI:10.18632/oncotarget.11039
PMID:27494875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5312390/
Abstract

BACKGROUND

Regulatory and cytotoxic T cells are key players in the host's anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+ cells to identify potential interactions.

METHODS

In 202 patients 103 pre-radiochemotherapy biopsies and 153 post-radiochemotherapy tumour specimens of advanced rectal cancer were available and an immunohistochemical double staining of FoxP3+ and CD8+ tumour-infiltrating lymphocytes was performed to investigate cell density and cell-to-cell distances.

RESULTS

FoxP3+ cells decreased after radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged. High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was associated with an improved overall survival. Cell-to-cell distances of randomly distributed cells were simulated and compared to observed cell-to-cell distances. Observed distances shorter than the simulated, random distances were hypothesized to represent FoxP3+ cells actively interacting with CD8+ cells. Epithelial short distances were associated with a favourable prognosis while the opposite was true for the stromal compartment.

CONCLUSION

The analysis of cell-to-cell distances may offer a tool to predict outcome, maybe by identifying functionally active, interacting infiltrating inflammatory cells in different tumour compartments.

摘要

背景

调节性T细胞和细胞毒性T细胞是宿主抗癌免疫反应的关键参与者。我们研究了FoxP+和CD8+细胞的空间分布，以确定潜在的相互作用。

方法

在202例患者中，有103例晚期直肠癌放疗前化疗活检标本和153例放疗后肿瘤标本，对FoxP3+和CD8+肿瘤浸润淋巴细胞进行免疫组织化学双重染色，以研究细胞密度和细胞间距离。

结果

放疗化疗后FoxP3+细胞减少了3倍，而CD8+细胞几乎保持不变。上皮（p=0.033）和基质（p=0.009）中高FoxP3+细胞密度与总生存期改善相关。模拟了随机分布细胞的细胞间距离，并与观察到的细胞间距离进行比较。观察到的距离短于模拟的随机距离被假设为代表FoxP3+细胞与CD8+细胞积极相互作用。上皮细胞间短距离与良好预后相关，而基质区则相反。

结论

细胞间距离分析可能提供一种预测预后的工具，也许是通过识别不同肿瘤区域中功能活跃、相互作用的浸润性炎症细胞来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/79ea6495685f/oncotarget-07-60383-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/b8d1d5b7fd38/oncotarget-07-60383-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/b3caf75d4903/oncotarget-07-60383-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/240056254b34/oncotarget-07-60383-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/5a5720713b9c/oncotarget-07-60383-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/f0e164781f99/oncotarget-07-60383-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/79ea6495685f/oncotarget-07-60383-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/b8d1d5b7fd38/oncotarget-07-60383-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/b3caf75d4903/oncotarget-07-60383-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/240056254b34/oncotarget-07-60383-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/5a5720713b9c/oncotarget-07-60383-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/f0e164781f99/oncotarget-07-60383-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f78/5312390/79ea6495685f/oncotarget-07-60383-g006.jpg

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