TNFRSF1B and neoplasm: On the one side, tTreg may expand at tumor site in response to self-antigens expressed by tumor cells, mostly include committed (TSDR-demethylated) Helios- and TNFR2-expressing cells, and contain the precursors of specialized T-bet+ Th1-suppressing cells, thus representing not only the guardians of systemic immune homeostasis but also the “hard core” of tumor immune escape.