Deregulation of the immune system in patients with chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) constitutes the most common leukemia in adults living in western countries. The clinical course of the disease is extremely heterogeneous and pathogenesis is still unknown. Immune system disorders in CLL patients are observed in the early stages of the disease and worsen during clinical observation. On the one hand, CLL patients are characterized by immunosupresion and on the other hand, autoimmune processes. The immunosuppression observed in patients with CLL is associated with disorders of non‑specific immune response as well as T‑cell and B‑cell response, leading to frequent and severe infections. The immune system of patients with CLL could be also inhibited by many immunosuppressive factors occurred in tumor microenvironment, including populations of immune cells, which include myeloid‑derived suppressor cells (MDSCs), T regulatory cells (Treg) and the newly described B regulatory cells (Breg). It was shown that CLL cells can regulate immune response and escape from the surveillance of the immune system through the PD‑1/PD‑L signalling pathway. Interestingly, reduced immune response in CLL patients may be accompanied by autoimmune processes clinically manifested as autoimmune cytopenias. The secondary autoimmune cytopenias complicating the course of the disease include autoimmune hemolytic anemia (AIHA), immune thrombocytopenia purpura (ITP), pure red cell aplasia (PRCA) and autoimmune granulocytopenia (AG). Identification of immunological disorders in patients with CLL is necessary to understand the biology of the disease and to select appropriate treatment patterns based on modulation of the immune system.