During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

Ekaterina Pylaeva; Georg Korschunow; Ilona Spyra; Sharareh Bordbari; Elena Siakaeva; Irem Ozel; Maksim Domnich; Anthony Squire; Anja Hasenberg; Kruthika Thangavelu; Timon Hussain; Moritz Goetz; Karl S Lang; Matthias Gunzer; Wiebke Hansen; Jan Buer; Agnes Bankfalvi; Stephan Lang; Jadwiga Jablonska

doi:10.1016/j.celrep.2022.111171

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

Cell Rep. 2022 Aug 16;40(7):111171. doi: 10.1016/j.celrep.2022.111171.

Authors

Ekaterina Pylaeva¹, Georg Korschunow², Ilona Spyra², Sharareh Bordbari², Elena Siakaeva², Irem Ozel², Maksim Domnich², Anthony Squire³, Anja Hasenberg³, Kruthika Thangavelu², Timon Hussain², Moritz Goetz⁴, Karl S Lang⁵, Matthias Gunzer⁶, Wiebke Hansen⁷, Jan Buer⁷, Agnes Bankfalvi⁴, Stephan Lang⁸, Jadwiga Jablonska⁹

Affiliations

¹ Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. Electronic address: [email protected].
² Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
³ Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
⁴ Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
⁵ Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
⁶ Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, 44139 Dortmund, Germany.
⁷ Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
⁸ Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Düsseldorf/Essen, 45147 Essen, Germany.
⁹ Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Düsseldorf/Essen, 45147 Essen, Germany. Electronic address: [email protected].

PMID: 35977505
DOI: 10.1016/j.celrep.2022.111171

Abstract

Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR⁺CD80⁺CD86⁺ICAM1⁺PD-L1^-) and stimulate T cells (CD27⁺Ki67^highPD-1^-). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1⁺ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy.

Keywords: CP: Cancer; CP: Immunology; T lymphocytes; adaptive immunity; antigen-presenting cells; cancer; head and neck cancer; immunosuppression; lymph nodes; metastasis; neutrophils; tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen*
Humans
Immunity
Lymph Nodes
Neoplasms* / pathology
Neutrophils

Substances

B7-H1 Antigen