Pylaeva, E.; Korschunow, G.; Spyra, I.; Bordbari, S.; Siakaeva, E.; Ozel, I.; Domnich, M.; Squire, A.; Hasenberg, A.; Thangavelu, K.; Hussain, T.; Goetz, M.; Lang, K. S.; Gunzer, M.; Hansen, W.; Buer, J.; Bankfalvi, A.; Lang, S.; Jablonska, J.
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+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.