Firstly, in comparison to SCC, ADC-enriched epithelial sub-clusters exhibited a higher propensity for interaction with Tregs through ligand-receptor signaling pathways, including ALCAM (ALCAM>>CD6) and MHC-II (HLA-DR>>CD4) (Figure 7A–E), which have been reported to be essential for Treg recruitment, expansion, and stabilization to establish the immunosuppressive microenvironment (Chalmers et al., 2022; Ferragut et al., 2021; Freitas et al., 2019). This evidence concerns the gene CD6 and AIDS dementia complex.