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01-11-2019 | Breast Cancer | Original Article

The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer

Authors: Michael Sofopoulos, Sotirios P. Fortis, Christoforos K. Vaxevanis, Nectaria N. Sotiriadou, Niki Arnogiannaki, Alexandros Ardavanis, Dimitrios Vlachodimitropoulos, Sonia A. Perez, Constantin N. Baxevanis

Published in: Cancer Immunology, Immunotherapy | Issue 11/2019

Abstract

Tumors and their surrounding area represent spatially organized “ecosystems”, where tumor cells and the immune contextures of the different compartments are in a dynamic interplay, with potential clinical impact. Here, we aimed to investigate the prognostic significance of peritumoral tertiary lymphoid structures (TLS) either alone or jointly with the intratumoral densities and spatial distribution of CD8 + and CD163 + cells in breast cancer (BCa) patients. TLS were identified peritumorally, within the area distancing up to 5 mm from the infiltrative tumor border, counted and further characterized as adjacent or distal, in formalin-fixed, paraffin-embedded tumor tissue samples from a cohort of 167 patients, with histologically confirmed invasive ductal BCa. TLS and tumor-infiltrating immune cells were determined by H&E and immunohistochemistry. Clinical follow-up was available for 112 of these patients. Patients with peritumoral TLS exhibited worse disease-free survival (DFS) and overall survival (OS) as compared to patients lacking TLS. Moreover, the density of peritumoral TLS was found to be crucial for prognosis, since patients with abundant TLS exhibited the worst DFS and OS. By combining the density of adjacent TLS (aTLS) with our recently published intratumoral signatures based on the differential distribution of CD8 + and CD163 + in the tumor center and invasive margin, we created two improved immune signatures with superior prognostic strength and higher patient population coverage. Our observations strengthen the notion for the fundamental role of the dynamic interplay between the immune cells within the tumor microenvironment (center/invasive margin) and the tumor surrounding area (peritumoral TLS) on the clinical outcome of BCa patients.

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Title: The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer
Authors: Michael Sofopoulos
Sotirios P. Fortis
Christoforos K. Vaxevanis
Nectaria N. Sotiriadou
Niki Arnogiannaki
Alexandros Ardavanis
Dimitrios Vlachodimitropoulos
Sonia A. Perez
Constantin N. Baxevanis
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 11/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02407-8

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