Changes in the immune system in untreated patients with chronic lymphocytic leukaemia – part 2: innate immune system

Overview

Chronic lymphocytic leukaemia (CLL), the most common leukaemia of adults in the western world, is associated with significant combined immunodeficiency. Besides changes in adaptive immunity, all components of innate immunity, both cellular i.e., NK cells, phagocytes and dendritic cells and humoral i.e., the complement cascade, can be affected. NK cells of CLL patients express less activation and more inhibitory receptors than those of healthy individuals. Together with changes in expression of these receptor ligands on CLL cells this prevents effective suppression of malignant clone proliferation by the immune system. Neutrophilic granulocytes have impaired ability of random migration, stimulated chemotaxis, respiratory burst or insufficient capacity of enzymes production and cytokine release. Other changes lead to the generation of so-called tumour associated neutrophils that suppress various cellular immunity components. Similarly, monocytes produce interleukin 10, transforming growth factor b and reactive oxygen species that lead to impairment of T-cell and NK cell function. Under the influence of CLL cells and regulatory T-cells, macrophages differentiate into nurse-like cells that attract CLL cells, support their survival and suppress non-regulatory T-cells. Dendritic cells are also affected by similar changes. Finally, complement defects can play a part in the development of not only infectious, but also autoimmune complications.

Keywords:

chronic – lymphocytic – leukaemia – immunodeficiency – cellular – humoral – NK – Granulocytes – Monocytes – Macrophages – dendritic – Complement – infections