CD4 and neoplasm: According to Savage et al. (2013), the biology of tumor-associated Treg cells involves two developmental pathways: (1) the recognition of self-antigen by developing thymocytes within the thymus leads to the development of naturally-occurring Foxp3+ Treg (nTreg) cells and (2), naïve CD4+ T cells recognize a tumor-associated or tumor-specific antigen at extrathymic sites and, after being activated, develop into an inducible Foxp3+ Treg cell (iTreg or Tr1) under a variety of conditions that facilitate/enable tumor immune evasion.