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

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 & mdash;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.

Automated summary

In this study, researchers found that tumor-associated neutrophils migrate to lymph nodes during head and neck cancer progression and play a dual role in shaping anti-tumor responses. In metastasis-free stages, neutrophils stimulate T cells, while in metastatic stages, they suppress T cell responses. The accumulation of neutrophils in lymph nodes can predict the survival rate of head and neck cancer patients.