MedWire News: Women with advanced breast cancer have fewer and less immunoresponsive dendritic cells than healthy individuals, study findings indicate.
The researchers also show that the immune response of these compromised cells can be boosted with CD40 ligand in vitro, offering hope for effective immunotherapies for breast cancer.
Dendritic cells are antigen-presenting cells that play a central role in initiating and directing antitumor immunity and are therefore important in the defense against cancer, explain José Alejandro López (Queensland Institute of Medical Research, Brisbane, Australia) and colleagues in the British Journal of Cancer.
Tumors employ numerous mechanisms to evade immune detection and elimination, however, including suppression of dendritic cells.
Studies have shown that women with elevated levels of dentritic cells have a better prognosis than other women, while researchers have demonstrated tumor-dendritic cell interactions in vitro.
López et al enrolled 239 women, of whom 78 had early breast cancer (T1N0M0), 59 had nodal stage breast cancer (T2N1M0), and 36 had advanced metstatic breast cancer (TNM1), along with 66 healthy controls.
The researchers measured levels of circulating dendritic cells 2 weeks prior to surgery then 6, 24, and 48 weeks post surgery using flow cytometry.
They found that women with metastatic breast cancer had 10 times fewer dentritic cells before surgery than healthy controls, while women with early and nodal stage breast cancer had more modest differences.
Over the course of a year, women with early stage breast cancer had a progressive 10-fold decline in dendritic cells, starting 6 weeks post surgery – an observation the researchers attribute to the affects of adjuvant chemotherapy.
The researchers also found that dendritic cells in breast cancer patients had impaired immune function – as determined by reduced levels of the cell surface proteins human leukocyte antigen (HLA)-DR and CD86, relative to healthy controls.
Finally, the researchers cultured these compromised dendritic cells in vitro and found that CD40 ligand was a potent stimulator of HLA-DR and CD86.
López et al caution, however: “While our findings advance [CD40 ligand] as one of the most potent stimuli for improving blood dendritic cells and further support its use to condition dendritic cells for breast cancer immunotherapy, its application in a clinical setting remains to be established.”
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