Credit: Monash University
New research may explain why patients with chronic lymphocytic leukemia (CLL) are vulnerable to severe, recurrent infections.
The study showed that plasmacytoid dendritic cells (pDCs), which orchestrate innate and adaptive immune responses, were eliminated in patients with aggressive CLL.
However, patients with a milder form of CLL appeared to have more pDCs, which suggests some protective effect.
Researchers reported these findings in Leukemia.
“These unprecedented findings reveal that these rare but critical cells can be restored at the experiment level, resulting in re-activated immune functions, including the destruction of cancer cells,” said study author Fabienne Mackay, PhD, of Monash University in Melbourne, Victoria, Australia.
“These results provide supporting evidence that a similar approach might have therapeutic benefits in patients with CLL.”
Dr Mackay and her colleagues noted that CLL patients’ vulnerability to infection is caused by a variety of immunological defects. But the initiating events of immunodeficiency in CLL are unclear.
To gain more insight, the researchers studied samples from CLL patients and conducted experiments in mouse models of the disease.
They found that, in progressive CLL, pDC numbers decreased, and their functionality was impaired. As a result, interferon alpha (IFNα) production decreased.
Additional investigation revealed that the decrease in pDCs and reduction in IFNα production resulted from decreased expression of FLT3 and TLR9.
However, the researchers were able to increase FLT3 expression using inhibitors of TGF-β and TNF. And this reduced the tumor load.
The team said these results offer new insight into mechanisms underpinning the immunodeficiency observed in CLL.
And they hope their discoveries will aid the development of new therapeutic strategies that reactivate the immune system and enhance the long-term survival of those CLL patients who are particularly vulnerable to fatal infectious complications.
