B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer

SIMPLE SUMMARY: Neutrophils exhibit multiple functions during cancer progression and are believed to regulate adaptive immune responses to cancer. In addition to their interactions with T cells in this context, these cells are also believed to interact with B cells. Neutrophils have been found in the marginal zone of the spleen, where they exhibit helper cell characteristics, supporting B cell proliferation and activation. Here, we investigate the effect of neutrophils on B cells in the regional lymph nodes (RLN) of head-and-neck cancer (HNC) patients. We have identified that, in RLNs, neutrophils express a helper cell phenotype that was associated with the increased activation and proliferation of B cells. Importantly, the high abundance of neutrophils in the B cell follicles of regional lymph nodes is associated with significantly improved HNC patient survival. ABSTRACT: The role of neutrophils during cancer formation and elimination is diverse. Here, for the first time, we investigate neutrophil helper cells (N(BH)), their influence on B cell activity in the regional lymph nodes (RLN) of head-and-neck cancer patients and the effect of this neutrophil/B cell interaction on patient prognosis. Circulating and RLN neutrophils of patients with stage I–IV head-and-neck squamous cell carcinoma were investigated with flow cytometry and qPCR. In addition, neutrophil/B cell co-localization in RLNs was evaluated using immunohistochemistry. B cell proliferation was assessed and correlated with the distance to neutrophils. Patient survival was evaluated. Neutrophils with the helper cell phenotype were identified in the RLN of HNC patients. B cells in close proximity to such N(BH) showed significantly higher proliferation rates, together with elevated activation-induced cytidine deaminase (AID) expression. Notably, patient survival was significantly higher in individuals with high N(BH) frequencies in the B follicles of RLNs. Neutrophils in RLN can support T cell-independent activation of the adaptive immune system through B cell stimulation, capturing helper cell phenotype character. The presence of such helper neutrophils in the RLNs of HNC patients positively correlates with patient prognosis.