CXCR4 and cancer: Figures 1D, E depicted the overall cell-cell interactions of the six cell clusters within HNSCC. Notably, fibroblasts and cancer cells presented the strongest output and input signals, suggesting their essential role in TME. A comparison of the communication between cancer cells and other cells in TME elucidated that MIF-CD74/CXCR4 and MIF-CD74/CD44 were the strongest Ligand-Receptor (LR) pairs between cancer cells and immune cells (Figure 1F).