CISH and neoplasm: Additionally, reduced responsiveness in leukocytes may reflect the effects of a high tumor burden whereby tumor cells secreting immunosuppressive cytokines, such as IL-10 and TGF-β, have been shown to induce expression of STAT1 negative regulators such as the suppressors of cytokine signaling (SOCS) proteins and Src homology 2 (SH2)-containing phosphatase-1 and -2 and CD45 [31-33], thereby inhibiting the anti-tumor activity of immune effector cells [34].