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Can TKIs Combined With Interferon-α Enhance Immunosuppressive State in CML?

By: Joshua Swore
Posted: Monday, March 2, 2020

Recent findings published in the Journal of Translational Medicine suggest that patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) and interferon-α may incur an enhanced immunosuppressive state. The research, which is the result of a collaboration between the University of Coimbra in Portugal and the University of Nottingham in United Kingdom, was conducted by Sergio Rutella, MD, PhD, of John van Geest Cancer Research Centre, Nottingham Trent University, and colleagues.

A total of 41 patients with CML and 20 controls were enrolled in the study. Patients with CML were divided into two treatment groups: TKIs alone (33 patients) and TKIs plus interferon-α (8 patients). Blood samples from all subjects were collected and used to analyze the number and types of immune cells present using a combination of flow cytometry and immunocytochemistry.

The authors found that patients who received TKIs plus interferon-α had fewer lymphocytes than healthy individuals (838/mL vs. 1,500/ mL; P = .017). In addition, the authors found a 50% increase in the number of regulatory T cells in patients treated with TKIs plus interferon-α compared with those treated with TKIs and controls (P =.001).

The researchers then quantified granulocytic myeloid-deprived suppressor cells. They found those who received the combination therapy had an increased number of these cells (21.3%) compared with controls, indicating that treatment may modulate the number of immune cells present in the blood. Lastly, researchers reported that patients who had received interferon-α had decreased levels of genes associated with immune cells, further indicating a suppressed immune state.

“Although the results need to be validated in a larger cohort of CML patients, the administration of IFN-α might be a valuable strategy to boost immune surveillance, to possibly eradicate leukemic stem cells, and to support TKI discontinuation, if associated with careful monitoring of immunosuppressive cells,” the investigators concluded.

Disclosure: The study authors reported no conflict of interests.



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