Abstract
Background:
Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact on TIM-3 and Gal-9 expression in CLL remains unclear.
Methods:
Peripheral blood mononuclear cells (PBMCs) from 20 treatment-naive CLL patients were cultured with or without IL-27 (100 ng/mL) for 72 h. Flow cytometry assessed TIM-3 and Gal-9 expression on CD4+, CD8+, and CD19+ cells.
Results:
IL-27 stimulation significantly increased TIM-3 expression on CD8+ T cells (2.18 ± 0.32% vs. 3.09 ± 0.49%, p = 0.009), a hallmark of T cell exhaustion. IL-27 also modestly increased intracellular Gal-9 levels in total lymphocytes (93.91 ± 1.17% vs. 96.55 ± 0.67%, p = 0.005). Additionally, IL-27 reduced CD4+ T cell proportions (26.71 ± 4.19% vs. 22.01 ± 3.23%, p = 0.010). Although numerically modest, these changes may be biologically pertinent in the context of checkpoint-mediated CD8+ T-cell exhaustion.
Conclusions:
IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study.