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, Ágnes Bánkfalvi, Stephan Lang, Jadwiga Jabłońska
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+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.