The adoptive transfer of defined antitumor effector lymphocytes in cancer immunotherapy stimulated the research towards novel approaches in activating lymphocytes in vitro. We previously found that in colon cancer patients serum level of soluble IL-2 receptor (sIL-2R) is significantly increased. In order to verify if this situation can affect the in vitro activation of peripheral blood mononuclear cells (PBMC), we examined their proliferative response to IL-2 and anti-CD3 monoclonal antibody (Mab) in patients. From our preliminary results, it is worth noting that the proliferative response to IL-2+anti-CD3 Mab is significantly higher that IL-2 alone in stage IV (p<0.001), where the sIL-2R is also significantly increased. Moreover, in other stages the proliferative response to IL-2+anti-CD3 Mab is not significantly different from IL-2 alone (p=0.49). The biological relevance of these results is still unclear. At present, further studies are in progress to determine the mechanism by which sIL-2R is related to IL-2+anti-CD3 Mab activation pathway and to examine potential physiological explanations.