We mainly focused on the tumor cells, CAFs, macrophages, and CD8+ T cells and obtained several original discoveries that were firstly demonstrated in HNSCC ecosystem: Firstly, fibroblasts from our samples were stratified in 8 clusters and 2 critical subpopulations (POSTN+ and RSPO1+ fibroblasts) showed distinct changes of both infiltrative proportions and biological functions during HNSCC stepwise progression. Here, RSPO1 is linked to neoplasm.