Detailed resolution analysis reveals spatial T cell heterogeneity in the invasive margin of colorectal cancer liver metastases associated with improved survival

• Verfasst von: Berthel, Anna [VerfasserIn]
• Verfasst von: Zörnig, Inka [VerfasserIn]
• Verfasst von: Valous, Nektarios A. [VerfasserIn]
• Verfasst von: Klupp, Fee [VerfasserIn]
• Verfasst von: Ulrich, Alexis [VerfasserIn]
• Verfasst von: Jäger, Dirk [VerfasserIn]
• Verfasst von: Halama, Niels [VerfasserIn]
• Titel: Detailed resolution analysis reveals spatial T cell heterogeneity in the invasive margin of colorectal cancer liver metastases associated with improved survival
• Verf.angabe: Anna Berthel, Inka Zoernig, Nektarios A. Valous, Christoph Kahlert, Fee Klupp, Alexis Ulrich, Juergen Weitz, Dirk Jaeger & Niels Halama
• E-Jahr: 2017
• Jahr: 23 Feb 2017
• Umfang: 11 S.
• Fussnoten: Gesehen am 04.06.2018
• Titel Quelle: Enthalten in: OncoImmunology
• Ort Quelle: Abingdon : Taylor & Franics, 2012
• Jahr Quelle: 2017
• Band/Heft Quelle: 6(2017,3) Artikel-Nummer e1286436, 11 Seiten
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2017.1286436
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Colorectal cancer liver metastases
• Sach-SW: immunosuppression
• Sach-SW: prognosis
• Sach-SW: T cell distribution
• Sach-SW: tumor immunology
• Sach-SW: tumor microenvironment
• K10plus-PPN: 1575915227

Abstract

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.