Our concise analyses on the spatial distribution of different T cell subsets and their association with cytokine levels in 84 well-characterized HNSCC tissues revealed that stromal Treg infiltration in p16− HNSCC could serve as an independent prognostic marker for improved patient survival, while higher CXCL10, IL-9, and CCL4 levels might be useful biomarkers to predict a deeper infiltration of T cells into tumor cell nests and thus to reach their potential target cells. Here, CCL4 is linked to head and neck squamous cell carcinoma.