Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer.
The generation of antitumour immunity depends on the nature of dendritic cell (DC)-tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy.
Pinzon-Charry
A
A
Dendritic Cell and Cancer Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. albertoP@qimr.edu.au
Ho
C S K
CS
Maxwell
T
T
McGuckin
M A
MA
Schmidt
C
C
Furnival
C
C
Pyke
C M
CM
López
J A
JA
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001773:Blood Cells; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D023201:CD40 Ligand / Q000502:physiology; D016022:Case-Control Studies; D002452:Cell Count; D003430:Cross-Sectional Studies; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000473:pathology; D009367:Neoplasm Staging; D010641:Phenotype
D017077:Culture Media, Conditioned; D023201:CD40 Ligand