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.
OBJECTIVE
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.


METHODS
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.
Li
Yan
Y
Institute of Oncology of Wuhan University & Department of Oncology, Mid-South Hospital of Wuhan University, Wuhan City, Hubei Province, 430071, China. liyansd@hotmail.com
Yang
Guo-Liang
GL
Yuan
Hong-Yin
HY
Bai
De-Jiao
DJ
Wang
Kun
K
Lin
Cong-Rao
CR
Hu
Ming-Bai
MB
Feng
Mao-Hui
MH
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D002927:Cimetidine / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007111:Immunity, Cellular; D007430:Intraoperative Care; D007694:Killer Cells, Natural / Q000473:pathology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011292:Premedication; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology
D000276:Adjuvants, Immunologic; D002927:Cimetidine