Pylaeva et al. studied neutrophil function in tumor-draining lymph nodes (LNs) during head and neck cancer (HNC) progression. A murine HNC model and LNs from HNC patients revealed that neutrophils from metastasis-free, early stages (N0) transmigrated to LNs, accumulated in T cell-rich zones and activated T cells in an antigen-dependent fashion. In late (N1-3) metastatic HNC, GM-CSF released from LN mets triggered neutrophils to express PD-L1 and become immunosuppressive. Five-year HNC survival data revealed a similar dual role: high LN neutrophil numbers positively predicted survival in early stages (N0), but a worse outcome in late stages (N1-3).
Contributed by Katherine Turner
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(high)PD-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.
Author Info: (1) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. Electronic address: ekaterina.pylaeva@uk-essen.de. (2) Department
Author Info: (1) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. Electronic address: ekaterina.pylaeva@uk-essen.de. (2) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (3) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (4) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (5) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (6) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (7) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (8) Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (9) Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (10) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (11) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. (12) Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. (13) Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. (14) Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; Leibniz-Institut fr Analytische Wissenschaften - ISAS - e.V, 44139 Dortmund, Germany. (15) Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. (16) Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. (17) Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. (18) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Dsseldorf/Essen, 45147 Essen, Germany. (19) Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Dsseldorf/Essen, 45147 Essen, Germany. Electronic address: jadwiga.jablonska@uk-essen.de.
