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

• Published in: Cell reports (Cambridge) Vol. 40; no. 7; p. 111171
• Main Authors: 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, Jadwiga
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 16.08.2022
• Subjects: adaptive immunity; antigen-presenting cells; cancer; head and neck cancer; immunosuppression; lymph nodes; metastasis; neutrophils; T lymphocytes; tumor; CP: Immunology; T lymphocytes; antigen-presenting cells; lymph nodes; head and neck cancer; metastasis; CP: Cancer; tumor; immunosuppression; cancer; neutrophils; adaptive immunity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111171

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. [Display omitted] •Tumor-associated neutrophils transmigrate to LNs and shape anti-cancer T cell response•In non-metastatic stage, LN neutrophils prime T cells and improve patient prognosis•Metastatic microenvironment via GM-CSF/STAT3 induces immunosuppressive neutrophils Pylaeva et al. show that neutrophils from tumors transmigrate to lymph nodes and shape anti-cancer T cell responses in head and neck cancer. In early non-metastatic stages, lymph node neutrophils prime anti-cancer T cells and improve patient prognosis. In metastatic stages, the metastatic microenvironment via GM-CSF/STAT3 induces immunosuppressive neutrophils.