Immune checkpoints PD1/PDL1, TIM3/GAL9 and key immune mediators landscape reveal differential expression dynamics on imatinib response in chronic myeloid leukemia.

The immune system of chronic myeloid leukemia (CML) patients is severely impaired, hampering anti-tumor responses, and maximal immune recovery occurs after achieving deep molecular responses to tyrosine kinase inhibitors. This study aimed to discern the expression patterns of NCR2, IL2, IL4, EOMES, FOXP3, GATA3, RORGT, PD1/PDL1 and TIM3/GAL9, expanding our previous dataset up to 19 key immune mediators, during the initial year on imatinib. Gene expression dynamics were evaluated in 171 peripheral blood samples from 89 CML patients, including 43 longitudinally monitored individuals, and 52 healthy donors. Univariate and unsupervised analyses confirmed diminished expression of most studied immune mediators, except for TNF, ARG1 and IL4, differentiating between baseline and 3-month samples. Most of the studied mediators normalized along treatment, with a transient increase of TNF and IL6 levels at 3-months, especially in optimal responders (BCR::ABL1 < 0.1%). Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.