Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients.
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.
Kubota
T
T
Department of Digestive Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
Fujiwara
H
H
Ueda
Y
Y
Itoh
T
T
Yamashita
T
T
Yoshimura
T
T
Okugawa
K
K
Yamamoto
Y
Y
Yano
Y
Y
Yamagishi
H
H
D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015738:Famotidine / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D018664:Interleukin-12; D015738:Famotidine; D002927:Cimetidine