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

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.

Relevant Cytokines in the B Cell Lymphoma Micro-Environment

“…The roles assigned to these example cytokines in the micro-environmental dialogue partially explain the compiled alterations in the blood levels of the corresponding cytokines owing to CLL and their normalization upon treatment with the BTK inhibitor ibrutinib. Finally, our commentary may support informed judgement on the article by Allegra et al [ 1 ].…”

“…Enhancing a recent review article published in this journal [ 1 ], the present discussion of paracrine interactions in the B cell lymphoma microenvironment emanates from evidence gained with in vitro cultures of different cell types. The chemokines CCL3 and CXCL12 represent contrasting examples of induced and constitutive production by tumor and bystander cells.…”

“…However, this heterogeneous group also includes, for instance, IL-8 and IL-34 that, according to their receptors, belong to other cytokine subgroups, namely chemokines and growth factors, respectively. Using the full spectrum of candidate cytokines without restriction to so-called ILs, unlike a recent review article [ 1 ], we selected examples of cytokines with relevance in B cell malignancies based on in vitro experiments involving lymphoma and bystander cells. After examples of chemokines that are predominantly produced by activated tumor cells, stromal fibroblasts or macrophages, we discuss cytokines that can be secreted by T cells and other cell types [ 3 , 4 ] and talk about myeloid bystander cells and the impact of colony stimulating factor 1 (CSF-1) on their development.…”

“…A recent review article about cytokines in chronic lymphocytic leukemia (CLL) [ 1 ] prompted us to provide an overview of the current understanding of the biological basis of cytokine production by various cell types and how this is reflected or not in the cytokine blood levels observed in CLL patients compared to healthy controls. For this purpose, we wish to outline the biological diversity of cytokines involved in B cell malignancies, the roles of selected cytokines in the micro-environmental dialogue, and how these roles may influence clinically observed blood levels of the respective cytokines.…”

Low Humoral Immune Response and Ineffective Clearance of SARS-Cov-2 in a COVID-19 Patient With CLL During a 69-Day Follow-Up

“…Liu et al ( 20 ) reported that the degree of lymphopenia and the severity of proinflammatory cytokine storms are increased in severe COVID-19 patients compared with those in patients with mild cases. Severe patients showed significant and sustained decreases in lymphocyte and T-cell counts and increases in IL-6, IL-10, IL-2, and IFN-γ levels, while mild cases exhibited increased neutrophil counts ( 12 , 21 ). The clinical characteristics in our case were consistent with the features of severe cases.…”