Phenotypic characterization of NK cells at the time of discontinuation and changes through time
non-relapsing
Among the forty-six patients enrolled in this study, seventeen (37%) lost MMR (We first compared NK cell proportions in AST patients and healthy donors (HD) (To determine if the absence of the TKI could affect the expression of these markers, patient samples at the time of discontinuation were compared with samples obtained three months after treatment interruption and analyzed regardless of patient clinical status (Comparison between NK cell markers from the time of discontinuation and three months after. Wilcoxon tests were performed (**** p<0.0001, *** p<0.001, ** p<0.01, *p<0.05).Next, our aim was to analyze the same panel of NK receptors in relapsing and non-relapsing patients at the time of discontinuation. By comparing the mean expression values between groups, no statistically significant differences were found for any of the activating receptors (CD16, NKG2C, NKG2D, NKp30, NKp44, NKp46), the inhibitory receptor NKG2A, CD158a/b from the Killer cell immunoglobulin-like receptor (KIR) family, the interleukin-2 receptor CD25 and the maturation marker CD57 (Percentage of NK cells and NK cell receptors at the time of discontinuation among relapsing and non-relapsing patients.NR (non-relapsed); R (relapsed); Median concentrations and range in percentage are listed. P-values were derived from Mann-Whitney test.Phenotypic characterization of NK cell markers from relapsing and non-relapsing patients. To assess how durable the immune profile could be, these comparisons were repeated with samples at 3 months after TKI cessation. Again, there were no statistically significant differences regarding the percentage of CD56dim (Considering that TKIs exert off-target effects on NK cells, and given that we have observed certain differences in the expression of several markers between the time of discontinuation and three months after, we thus wondered if the absence of the inhibitor affected relapsed and non-relapsed patients differently and if those differences could help to identify future relapses. Remarkably, several markers were down or upregulated between the time of discontinuation and the first three months off-TKI (Percentage of NK cells and NK cell receptors in relapsed and non-relapsed patients at the time of discontinuation and three months after.M0 (month 0, time of discontinuation); M3 (month 3 after discontinuation); Median concentrations and range in percentage are listed. P-values were derived from Wilcoxon test. Bold values correspond to statistically significant results (p < 0.05) and receptors that share the same behavior between relapsed and non-relapsed patients.