Treg exhaustion has frequently been reported in malignancies where checkpoint blockade through PD-1 is an effective tumor treatment.40 miR-15/16fl/flFoxp3Cre Tregs were characterized by high PD-1 expression, a feature associated with exhaustion, IFN-γ production, and reduced suppression of CD4+ Teff cells.41 miR-15/16fl/flFoxp3Cre mice displayed increased numbers of Teff cells and elevated IFN-γ production, indicating possible Treg dysfunction related to cell exhaustion. This evidence concerns the gene CD4 and neoplasm.