Dendritic cells are dysfunctional in patients with operable breast cancer.
BACKGROUND
Dendritic cells (DCs) play a crucial role in presenting antigens to T lymphocytes and inducing cytotoxic T cells. DCs have been studied in patients with breast cancer to define the factors leading to failure of an effective systemic and locoregional anticancer host response.


METHODS
Purified DCs were obtained from peripheral blood (PB) and lymph nodes (LNs) of women with operable breast cancer, using immunomagnetic bead selection. The stimulatory capacity of DCs in the allogeneic mixed leukocyte reaction (MLR) and autologous T cell proliferation test (purified protein derivative (PPD) as stimulator), the expression of surface markers on DCs and the production of cytokines in vitro by DCs from patients with operable breast cancer and from healthy donors (controls) were studied.


RESULTS
70-75% purified DCs were isolated from PB and LNs. PBDCs and LNDCs from patients with operable breast cancer demonstrated a reduced capacity to stimulate in an MLR, compared with PBDCs from normal donors (p<0.01). Autologous T cell proliferation in patients had a decreased ability to respond to PPD, when compared with controls (p<0.01). However, T cells from patients responded as well as control T lymphocytes in the presence of control DCs. PBDCs and LNDCs from patients expressed low levels of HLA-DR and CD86, and induced decreased interleukin-12 (IL-12) secretion in vitro, compared with DCs from normal donors (p<0.01).


CONCLUSIONS
These data suggest a defective DC function in patients with operable breast cancer. Switched-off DCs in patients with early breast cancer and decreased IL-12 production may be important factors for progressive tumour growth.
Satthaporn
Sukchai
S
Section of Surgery, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
Robins
Adrian
A
Vassanasiri
Wichai
W
El-Sheemy
Mohamed
M
Jibril
Jibril A
JA
Clark
David
D
Valerio
David
D
Eremin
Oleg
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D001943:Breast Neoplasms / Q000276:immunology / Q000503:physiopathology*; D016022:Case-Control Studies; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014373:Tuberculin / Q000494:pharmacology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D014373:Tuberculin; D018664:Interleukin-12