TGFB1 and neoplasm: In conclusion, during initiation as well as after chemotherapy, when NSCCs are not present in the tumor microenvironment, CSCs, albeit present in low numbers, generate immunosuppressive CD4+CD25+FOXP3+ Treg cells in a contact-independent manner by shedding high levels of immune-suppressive Treg-polarizing cytokine TGFβ, thus escaping immune-elimination and initiating the tumor or causing tumor relapse.