Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial.

BACKGROUND/AIMS: Cimetidine (CIM) seems to have positive effects on the immune systems of cancer patients. This study was conducted to investigate the effects of perioperative administration of CIM on the peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODOLOGY: Forty-nine GI cancer patients were randomized into a treatment group which took CIM in the perioperative period, and a control group which did not take the drug. The treatment was initiated 7 days (d) before operation and continued until 10 d after surgery. At baseline examination, before operation, on the 2nd and the 10th postoperative d, peripheral blood T lymphocytes, helper T cells, T suppressor cells, and NK cells were measured by immunocytochemical method. The surgical specimens were examined for TIL response, and immunohistochemical study was performed to measure the proportion of T and B lymphocytes in the TIL population. RESULTS: In comparison with normal controls, both the treatment and the control groups had decreased T cells, helper T cells and NK cells at baseline. In the control group, total T cells, helper T cells and NK cells declined progressively with the disease course and the decreases became more profound after operation. From the baseline to the 2nd postoperative d, the proportion of total T cells, helper T cells, and NK cells went down from 60.5+/-4.6 to 56.2+/-3.8 percent, from 33.4+/-3.7 to 28.1+/-3.4 percent, and from 15.0+/-2.8 to 14.2+/-2.2 percent, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative d, the treatment group had significantly higher percentages of total T cells, helper T cells and NK cells than control group. Moreover, CIM treatment also boosted the TIL response, as was reflected by findings that 68% (17/25) of the patients in the treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL response. CONCLUSIONS: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity boost TIL responses to tumor.

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results of a randomized controlled clinical trial.

AIM: To study the effects of perioperative administration of cimetidine (CIM) on peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS: Forty-nine GI cancer patients were randomized into treatment group, who took CIM in perioperative period, and control group, who did not take the drug. The treatment was initiated 7 days before operation and continued for 10 days after surgery. At baseline examination before operation, on the 2nd and 10th postoperative days, total T lymphocytes, T helper cells, T suppressor cells, and NK cells in peripheral blood were measured respectively by immunocytochemical method using mouse-anti human CD(3), CD(4), CD(8) and CD(57) monoclonal antibodies. Blood samples from 20 healthy volunteers were treated in the same way as normal controls. Surgical specimens were examined during routine histopathological evaluation for the presence of TIL in tumor margin. Immunohistochemical study was performed to measure the proportion of T and B lymphocytes in TIL population. T and B lymphocytes were detected respectively using mouse-anti-human CD(3) and CD(20) monoclonal antibodies. RESULTS: In comparison with normal controls, both the treatment and control groups had decreased T cells, T helper cells and NK cells at baseline. In control group, total T cells, T helper cells and NK cells declined continuously with the disease progression and the decrease became more obvious after operation. From baseline to the 2nd postoperative day, the proportion of total T cells, T helper cells, and NK cells went down from 60.5+/-4.6% to 56.2+/-3.8%, 33.4+/-3.7% to 28.1+/-3.4%, and 15.0+/-2.8% to 14.2+/-2.2%, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative day, the treatment group had significantly higher percentages of total T cells, T helper cells and NK cells than control group. Moreover, CIM treatment also boosted TIL response, as was reflected by findings that 68% (17/25) of the patients in treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL responses (P<0.01). CONCLUSION: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity induced by tumor burden and surgical maneuver. The drug could also boost TIL responses to tumor. These effects suggest that the drug be used as an immunomodulator for GI cancer patients.