Detailed resolution analysis reveals spatial T cell heterogeneity in the invasive margin of colorectal cancer liver metastases associated with improved survival
On a broader scale, T cell density and localization in colorectal cancer liver metastases have prognostic and predictive implications. As T cell distribution at higher resolutions has not been fully investigated, a detailed resolution analysis of T cell distribution was performed. Patient tissues we...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 Feb 2017
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| In: |
OncoImmunology
Year: 2017, Jahrgang: 6, Heft: 3 |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2017.1286436 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1080/2162402X.2017.1286436 Verlag, kostenfrei, Volltext: https://doi.org/10.1080/2162402X.2017.1286436 
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| Verfasserangaben: | Anna Berthel, Inka Zoernig, Nektarios A. Valous, Christoph Kahlert, Fee Klupp, Alexis Ulrich, Juergen Weitz, Dirk Jaeger & Niels Halama |
| Zusammenfassung: | On a broader scale, T cell density and localization in colorectal cancer liver metastases have prognostic and predictive implications. As T cell distribution at higher resolutions has not been fully investigated, a detailed resolution analysis of T cell distribution was performed. Patient tissues were divided into 10 µm distance classes between the tumor border and adjacent normal liver. Thereby, distinct density patterns of T cell localization in relation to the malignant tissue could be detected. At a distance of 20 to 30 µm to the tumor, a decrease of CD3 T cells is common. Within this area, cytotoxic Granzyme B and CD8+ T cells were found to be significantly reduced as well as CD163 macrophages were increased and identified to be in close contact with T cells. Our data suggests a physical or functional border within this region. Survival analysis revealed improved overall survival in patients with high T cells numbers at the direct tumor border. Interestingly, the decreased T cells in the 20 to 30 µm region were also found to be significantly associated with improved survival. Consequently, the detailed localization of T cells, despite blockade, could be associated with improved clinical outcome. The high-resolution analysis represents new insights into relevant heterogenous T cell distributions especially related to clinical responses. As the paradoxical observation of localization-dependent prognostic relevance of T cell densities is only detectable by detailed spatial analyses, this investigation of spatial profiles at higher resolutions is suggested as a new biomarker for survival and response to therapies. |
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| Beschreibung: | Gesehen am 04.06.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2017.1286436 |