Immune checkpoints PD1/PDL1, TIM3/GAL9 and key immune mediators landscape reveal differential expression dynamics on...

Area of Science:

• Immunology
• Hematology
• Oncology

Background:

• Chronic myeloid leukemia (CML) is characterized by immune system impairment, affecting anti-tumor responses.
• Maximal immune recovery in CML patients is linked to deep molecular responses achieved with tyrosine kinase inhibitors (TKIs).

Purpose of the Study:

• To investigate the dynamic expression patterns of 19 key immune mediators in CML patients during their first year of imatinib treatment.
• To correlate immune gene expression profiles with treatment response and molecular outcomes in CML.

Main Methods:

• Gene expression analysis of 19 immune mediators in 171 peripheral blood samples from 89 CML patients and 52 healthy donors.
• Longitudinal monitoring of 43 CML patients over a one-year period on imatinib therapy.
• Univariate, unsupervised, and multivariate analyses to assess gene expression dynamics and treatment response.

Main Results:

• Most immune mediators were initially diminished in CML patients, with exceptions like TNF, ARG1, and IL4.
• Immune mediator levels generally normalized during treatment, with transient increases in TNF and IL6 at 3 months, particularly in optimal responders.
• Non-optimal responders showed elevated ARG1 and a shift from PD1/PDL1 to TIM3/GAL9 immune checkpoint dominance over 12 months.

Conclusions:

• Longitudinal immune gene expression profiling in CML patients on imatinib provides insights into immune recovery dynamics.
• Immune mediator expression patterns, particularly ARG1 and immune checkpoints, may distinguish between optimal and non-optimal treatment responses in CML.
• Understanding these immune dynamics could inform therapeutic strategies and improve outcomes for CML patients.