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Identifying Pathologic Characteristics of NKT-Like Cells in Patients Treated for CML

By: Joseph Fanelli
Posted: Thursday, December 19, 2019

In an analysis of patients diagnosed with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), investigators found a decrease in NKT-like cells, as well as higher cytotoxicity, and different patterns of membrane receptors; these findings were published in Frontiers in Immunology. “Major differences” in receptor expression were associated with activation, tumor recognition, and immune regulation, concluded Paulo Rodrigues-Santos, PhD, of the Institute of Immunology at the University of Coimbra, Portugal, and colleagues.

“Further studies are needed to clarify the role of these cells as biomarkers of therapy response and also to evaluate their value for discrimination of better candidates for sustained treatment-free remission after TKI discontinuation,” the authors concluded.

In this trial, the authors analyzed peripheral blood NKT-like cells from 48 patients with CML and 40 healthy donors. Functional tests of co-culture with leukemic target cells (K562 cell line) were employed to measure degranulation and cytokine production.

The authors found that NKT-like cells were decreased in patients with CML, although these patients exhibited increased expression of activation markers (CD69 and HLA-DR), increased degranulation (CD107a), and impaired IFN-γ production. In patients with CML, NKT-like cells caused alterations on the expression of tumor-recognition receptors (NCRs and NKp80) and immune-regulation receptors (LAG-3, TIM-3, and CD137).

In cases of treatment with second-generation TKIs, NKT-like cells increased cell activation (CD69) and decreased expression of NKp44 and NKp80 when compared with imatinib. Additionally, patients with CML presented downregulation of NKp44 and LAG-3 after achieving deep molecular responses. “Those could represent potential markers for sustained treatment-free remission after discontinuation,” the authors noted.

Disclosure: For full disclosures of the study authors, visit frontiersin.org.



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