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- ItemDuring early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes(Maryland Heights, MO : Cell Press, 2022) Pylaeva, Ekaterina; Korschunow, Georg; Spyra, Ilona; Bordbari, Sharareh; Siakaeva, Elena; Ozel, Irem; Domnich, Maksim; Squire, Anthony; Hasenberg, Anja; Thangavelu, Kruthika; Hussain, Timon; Goetz, Moritz; Lang, Karl S; Gunzer, Matthias; Hansen, Wiebke; Buer, Jan; Bankfalvi, Agnes; Lang, Stephan; Jablonska, JadwigaTumor-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+Ki67highPD-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.