Impaired function of circulating dendritic cells in patients with pancreatic cancer.
OBJECTIVE
Dendritic cells (DCs) are important for immune surveillance and play a central role in protection against infection and malignancy. DCs comprise two subsets: DC1 (myeloid DC) and DC2 (lymphoid DC). The aim of this study is to determine whether the number and/or function of circulating DCs were decreased in patients with pancreatic cancer and to evaluate the effects of these changes in patients with locally advanced pancreatic cancer before and after chemoradiotherapy (CRT). We examined the circulating DC number and function using the peripheral blood from 29 patients with pancreatic cancer and 20 healthy control subjects. In patients who underwent CRT (n = 20), blood samples were taken before and after CRT. DCs were tested for the ability to stimulate allogeneic T lymphocytes in mixed leukocyte reaction (MLR). CD4/8, NK activity, PHA, and TGF-beta1 were also measured.


RESULTS
The number and allostimulatory activity of circulating DC1s in patients were significantly lower than those in controls. In the patients who underwent CRT, the allostimulatory activity of DC1s at post-CRT was significantly increased as compared to those at pre-CRT. The level of TGF-beta1 was also significantly decreased at post-CRT as compared to pre-CRT. There were no changes in CD4/8, NK activity and proliferative response of T lymphocytes at the peri-CRT period.


CONCLUSIONS
These data indicate that the number and function of circulating DCs were impaired in patients with pancreatic cancer. Chemoradiotherapy, however, improved DC function, which might be related to decreased immunosuppressive cytokine levels.
Yanagimoto
Hiroaki
H
Department of Surgery, Kansai Medical University, Osaka, Japan. yanagimh@takii.kmu.ac.jp
Takai
Soichiro
S
Satoi
Sohei
S
Toyokawa
Hideyoshi
H
Takahashi
Kanji
K
Terakawa
Naoyoshi
N
Kwon
A-Hon
AH
Kamiyama
Yasuo
Y
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002452:Cell Count; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1
D000970:Antineoplastic Agents; D006684:HLA-DR Antigens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12