Abstract
Simple SummaryIn chronic lymphocytic leukemia (CLL), immune alterations—affecting both the innate and adaptive immunity—are very common. As a clinical consequence, patients with CLL frequently present with autoimmune phenomena, increased risk of infections and second malignancies. The aim of this review article is to present available data on CLL-associated alterations of immune parameters that correlate with known prognostic markers and with clinical outcome. Also, data on the impact of immune-related clinical manifestations on the prognosis of patients with CLL will be discussed.Chronic lymphocytic leukemia (CLL) is characterized by a wide spectrum of immune alterations, affecting both the innate and adaptive immunity. These immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course. Quantitative and functional alterations involving conventional T cells, γδ T cells, regulatory T cells, NK and NKT cells, and myeloid cells, together with hypogammaglobulinemia, aberrations in the complement pathways and altered cytokine signature have been reported in patients with CLL. Some of these immune parameters have been shown to associate with other CLL-related characteristics with a known prognostic relevance or to correlate with disease prognosis. Also, in CLL, the complex immune response dysfunctions eventually translate in clinical manifestations, including autoimmune phenomena, increased risk of infections and second malignancies. These clinical issues are overall the most common complications that affect the course and management of CLL, and they also may impact overall disease prognosis.
Highlights
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease typically characterized by a wide spectrum of immune alterations, affecting both innate and adaptive immunity
The aim of this review article is to present available data on immune parameters which are altered in patients with CLL, and that can associate with other disease characteristics with a known prognostic relevance or that directly correlate with prognosis (Figure 1)
We find anti-CD20 monoclonal antibody-based therapies, whose anti-tumor activity is strongly linked to the Natural Killer (NK) cell-related antibody-dependent cell-mediated-cytotoxicity (ADCC)
Summary
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease typically characterized by a wide spectrum of immune alterations, affecting both innate and adaptive immunity (reviewed in [1]). Several studies have reported that T lymphocytes from patients with CLL are primed for anergy because of their higher expression of immune-checkpoint molecules, such as CTLA-4 [32], PD-1 [18,33], LAG3 [34], Tim-3 [35], TIGIT [36], CD160 and CD244 [37], leading to a microenvironment characterized by reduced T-cell proliferation, killing ability and cytokine release Of note, both CD8+ and CD4+ T-cell subsets show a complex co-expression of molecules indicating T-cell exhaustion (PD-1), senescence (KLRG-1) and activation (HLA-DR) [15]. Among previously treated patients, those with advanced disease stages showed an increased PD1+, Tim-3+ and TIGIT+ T-cell counts [35] In line with these data, Jimenez et al recently reported that patients who are in clinical progression present an accumulation of terminally exhausted effector CD8+ T cells, which are characterized by the co-expression of PD-1, CD244 and CD160 inhibitory receptors and by an altered gene expression profile [38]. These findings support the concept that tumor-induced chronic activation fosters the undesired accumulation of immune cells inadequate for an effective antitumor activity
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