In summary, the two immune-related HNSCC fibroblast subtypes occupy distinct immunological niches; FRC-like are found in TLS with CD4 + T-cells and B-cells and regulated through non-canonical NF-κB signalling via LTBR; iCAF are found with inflammatory monocytes and neutrophils and regulated through canonical NF-κB signalling through TNF-α and IL-1β. Here, CD4 is linked to head and neck squamous cell carcinoma.