Discussion
cancer
CANCER, CML, REMISSION
The mechanisms behind successful TFR are still unclear. Here, we were able to investigate systematically the frequencies of specific NK cell subpopulations, in sustained remission after treatment cessation. In our study, increased molecular relapse-free survival was associated with higher percentages of CD56None of the remaining markers were differentially expressed between relapsed and non-relapsed patients, which could indicate that patients included in our study present NK cells with a competent phenotype. Nevertheless, thanks to having consecutive samples during the trial, we were able to evaluate the dynamics of their expression over time. The only receptor that showed differences between groups was NKp44 at month 3, a NCR only present on activated or cytokine stimulated NK cells, in contrast to NKp30 and NKp46 that are constitutively expressed on resting NK cells. Our results indicate higher expression of NKp44 in the relapsed group and better relapse-free survival in patients with lower expression of this marker. The role of this receptor in cancer is poorly understood, but it is well known that it can be expressed in three transcriptional variants that differ in the length of the cytoplasmic domain. The NKp44-1 isoform containing an ITIM motif has the potential for both inhibitory and activating signalling (To our knowledge, our study is the first to describe this subset of NK cells with overall increased degranulation capacity, which appears to confer certain protective capacity for patients who do not relapse. However, the clinical impact of NK cells in patients who discontinued TKIs remains controversial, and further studies in a larger cohort are still needed. Finally, our results suggest that enhancing or restoring NK immune effector functions may be a strategy to increase the rate of successful TFR in CML.