Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment

Schmidt E, Distel L, Erber R, Büttner-Herold M, Rosahl MC, Ott O, Strnad V, Hack C, Hartmann A, Hecht M, Fietkau R, Schnellhardt S (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Cancers MDPI

Book Volume: 16

Article Number: 3160

Journal Issue: 18

DOI: 10.3390/cancers16183160

Abstract

Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs.

Authors with CRIS profile

Eva Schmidt Lehrstuhl für Strahlentherapie Luitpold Distel Department of Radiation Oncology Ramona Erber Institute of Pathology Maike Büttner-Herold Department of Nephropathology Oliver Ott Lehrstuhl für Strahlentherapie Vratislav Strnad Department of Radiation Oncology Carolin Hack Lehrstuhl für Geburtshilfe und Frauenheilkunde Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Rainer Fietkau Lehrstuhl für Strahlentherapie

Involved external institutions

Universitätsklinikum des Saarlandes (UKS) DE Germany (DE)

How to cite

APA:

Schmidt, E., Distel, L., Erber, R., Büttner-Herold, M., Rosahl, M.-C., Ott, O.,... Schnellhardt, S. (2024). Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment. Cancers, 16(18). https://doi.org/10.3390/cancers16183160

MLA:

Schmidt, Eva, et al. "Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment." Cancers 16.18 (2024).

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