Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity
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Rebecca Posselt1,*, Katharina Erlenbach-Wünsch2,*, Matthias Haas3, Jonas Jeßberger1, Maike Büttner-Herold4, Marlen Haderlein1, Markus Hecht1, Arndt Hartmann2, Rainer Fietkau1, Luitpold V. Distel1
1Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
2Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
3Department of Radiology, Charité Universitätsmedizin, Berlin, Germany
4Deparment of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
*These authors have contributed equally to this work
Luitpold V. Distel, email: Luitpold.Distel@uk-erlangen.de
Keywords: regulatory T cells, cytotoxic T cells, FoxP3+, CD8+, tumour-infiltrating lymphocytes
Received: May 10, 2016 Accepted: July 19, 2016 Published: August 03, 2016
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.
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