Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role.

Alessandro Allegra,Giovanni Pioggia,Caterina Musolino,Alessandro Tonacci,Marco Casciaro,Sebastiano Gangemi

doi:10.3390/cancers12020524

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is the main cause of mortality among hematologic diseases in Western nations. B-CLL is correlated with an intense alteration of the immune system. The altered functions of innate immune elements and adaptive immune factors are interconnected in B-CLL and are decisive for its onset, evolution, and therapeutic response. Modifications in the cytokine balance could support the growth of the leukemic clone via a modulation of cellular proliferation and apoptosis, as some cytokines have been reported to be able to affect the life of B-CLL cells in vivo. In this review, we will examine the role played by cytokines in the cellular dynamics of B-CLL patients, interpret the contradictions sometimes present in the literature regarding their action, and evaluate the possibility of manipulating their production in order to intervene in the natural history of the disease.

Highlights

NF-kB phosphorylation in T and B cells from B-cell chronic lymphocytic leukemia (B-Chronic lymphocytic leukemia (CLL)) patients. All of these findings indicate that the phenotype of Th17 cells in B-CLL patients is different from that in healthy subjects, presenting greater concentrations of IL-17F, and that lymphocytes from B-CLL patients are intensely reactive to IL-17F
In the study, the authors recognized new genes, chemokine (C-C motif) ligand 2, and pathways, nuclear respiratory factor-2 (NRF2)-mediated oxidative stress response signaling. Their findings suggest that CCL2 and possibly other inflammatory cytokines are implicated in B-CLL cell survival in vitro, and they might be relevant in vivo as well
B-CLL is characterized by increased monoclonal B lymphocytes, whose proliferation and persistence necessitate endogenous and exogenous stimulation elements [225,226]

Summary

Introduction

Its serum concentrations are augmented in B-CLL patients compared to healthy controls, and it has been demonstrated that IL-8 increases B-CLL cell survival [104,105,106,107,108]. IL-15 demonstrates relevant physiological actions in assisting with innate and adaptive immunity [152] It has a central role in the stimulation of T lymphocytes and NK cells, increasing cytotoxic functions, stimulating IFN-g, TNF-a, and GM-CSF production, and regulating macrophage/NK relations [153,154]. Browning et al reported that treating B-CLL cells with the ODN CpG-685 caused the overexpression of the IL-21 receptor This elevation increased the effects of IL-21 by significantly affecting JAK1, STAT1, and STAT3 phosphorylation compared to IL-21 therapy without activating. The stage of leukemia did not change the spontaneous programmed cell death in vitro [211]

Future Perspectives

Conclusions