NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance

In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56bright and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors NKp30 and NKp46.

Dr. Anna Martner from the TIMM Laboratory, Sahlgrenska Cancer Center at the University of Gothenburg in Gothenburg, Sweden said, "At diagnosis, approximately 70% of patients with acute myeloid leukemia (AML) are >60 years old. While a high proportion of older patients achieve complete remission (CR) after chemotherapy, leukemia relapse is common in the post-chemotherapy phase and significantly explains why the rates of 5-year survival of older patients are in the range of 10–15%"

Several aspects of NK cell function are reportedly relevant to AML prognosis, but a systematic analysis of aspects of NK cell biology in older patients has not been carried out.

Figure 1: Induction and activation of NK cells in patients below and above 60 years of age. The box plots in panel A-F show the number of CD16⁺ or CD56^bright NK cells in blood A and D. and the median fluorescence intensity (MFI) of NKp30 B and E. and NKp46 C and F. on CD16⁺ or CD56^bright NK cells before (C1D1) and after (C1D21) the first 21-day treatment cycle with HDC/IL-2 in patients <60 years (young, white; NK cell counts, n = 17, NCR expression, n = 21) and >60 years (old, grey; NK cell counts, n = 30, NCR expression, n = 35). Induction of NK cell counts and NCR expression were analyzed using Student's paired t-test.

Human NK cells comprise two main phenotypes: the cytotoxic CD16+/56+ NK cells constitute 90 95% of blood NK cells in healthy subjects, whereas the weakly cytotoxic CD16 /56bright cells are regarded as precursors of CD16+ NK cells.

NK cell cytotoxicity is regulated by activating and inhibitory NK cell receptors and their cognate ligands on malignant target cells.

The Martner Research Team concluded that while NCR ligands are frequently expressed by malignant AML cells, NK cells of newly diagnosed AML patients may express lower densities of NCR, which impacts on the anti-leukemic efficiency of NK cells as well as on survival and the likelihood of achieving CR after chemotherapy.

Full text - https://doi.org/10.18632/oncotarget.5559

Correspondence to - Anna Martner - [email protected]

Keywords - acute myeloid leukemia, immunotherapy, natural killer cells, NKp30, NKp46