Strikingly, interactions between the TIGIT receptor in lymphocytes (e.g., TREG and CD8TEREX) and NECTIN2/3 ligands in dendritic, mesenchymal and endothelial cells were found at C4 of breast cancer, but not at C9 and C15 stages of preneoplastic BRCA1+/mut breast tissues, showing the multiple immunosuppressive signals in the Breast-C4 TME. The gene discussed is NECTIN2; the disease is breast cancer.