Clinical Implications of Immune Dysfunction in Chronic Lymphocytic Leukemia

The immunosuppression inherent to chronic lymphocytic leukemia (CLL) is the most frequent cause of morbidity and mortality associated with this pathology. Both the innate and adaptive immune responses exhibit marked functional alterations, with a bias towards a tolerant environment that favors the spread of the disease. This condition is reflected in increased risk of infections, immune-mediated cytopenias, and associated second malignancies. Knowledge of these alterations, both in the molecular pathways that modulate T cell activity in CLL (the T lymphocyte cytotoxic antigen-4 (CTLA-4) axis and programmed cell death 1 (PD-1)) and at the T cell immunoreceptor level, could be of interest as therapeutic targets in CLL. In this review, we will analyze the main consequences of this dysfunction and its management strategies.