Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients

Abstract

Cimetidine, a H 2 receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [ 3 H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H 2 receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.

Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats

“…Cimetidine has demonstrated immunomodulatory effects in a number of studies (32)(33)(34)(35)(36), while histamine has been shown to have immunosuppressive effects (37,38). These results suggest that the effect of cimetidine on immunity is mediated by blocking the immunosuppressive effect of histamine via the H 2 receptor.…”

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

“…Since circulating T lymphocytes and NK cells are major defense mechanisms against tumor cells released into the circulation, and TIL is one of the most crucial factors restricting local tumor growth and progression, it is desirable to use it as an immunomodulator in the perioperative period. Moreover, since CIM has many other favorable effects besides immunomodulation on lymphocytes, such as activating macrophages, increasing tumor inhibitory cytokines [49] , enhancing the antigen presenting capacity of dendritic cells [60] , reducing tumor cell proliferation, inhibiting tumor cell metastasis via anti-adhesion mechanisms [49] and increasing the overall survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumor cells [61] , it is therefore advisable to use this low cost, convenient and almost nontoxic drug as a practical immunity-enhancing measure for GI cancer patients.…”

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

“…An accumulating body of evidence suggests that this drug may improve the survival of patients with different malignancies, and its antitumor effect is mediated at least in part by immune mechanisms. In particular, cimetidine-mediated immunomodulation is based on the the enhancement of antigen-presenting DC activity, 113 inhibition of suppressor T lymphocyte activity 114 and MDSC activity, 115 stimulation of NK cell activity 116 and increase in IL-2 production in helper T lymphocytes. 117 Another H2-antagonist famotidine has been found to stimulate IL-2-driven LAK activity beneficial for the treatment of renal cancer.…”