Tumor-associated neutrophils and macrophages differentially affect T-cell biology in the head and neck cancer tumor...

Intra-tumoral T-cell activity is required for effective antitumor immune responses and is partly regulated by tumor-associated neutrophils and macrophages. Here, we investigated the spatial context of neutrophil/macrophage interactions with CD8+ T cells in head and neck squamous cell carcinoma. Using multiplex immunofluorescence staining of biopsy specimens from 14 patients, we analyzed neutrophils, macrophages, and CD8+ T cells within tumor nests and stromal compartments. All 3 cell types were enriched in the stroma. To characterize spatial immune niches, we defined regions enriched for each cell type and analyzed their overlap. CD8+ T cells showed spatial exclusion from neutrophils, whereas macrophages colocalized with CD8+ T cells. In regions enriched for both neutrophils and CD8+ T cells, neutrophils were associated with reduced CD8+ T-cell proliferation, potentially caused by contact-dependent suppression. These findings demonstrate that neutrophils and macrophages differentially shape CD8+ T-cell distribution and activity within the head and neck cancer microenvironment.