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A letter in the Blood Cancer Journal discusses a study that explored a new approach to preserving lymphoid functionality in patients with chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL). The study found that BET cell treatment, which involves expanding T-cells in the laboratory, was safe and feasible for CLL and iNHL patients. The treatment led to a significant increase in T-cell count one month after infusion, indicating early T-cell recovery. The study also observed the preservation of T-cell subpopulations and CMV-specific CD8+ cells during the expansion process. The findings suggest that BET cell therapy may promote immune reconstitution and could be used to obtain leukemia-free T-cells for CAR-T cell production. [Extracted from the article]

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults. It is the clonal expansion of B cells expressing CD19 and CD5. Despite significant progress in treatment, CLL is still incurable. γδ T cells comprise an important subset of the cytotoxic T cells. Although γδ T cells in CLL are dysfunctional, they still can possibly be used for immunotherapy. The current paper reviews our understanding of γδ T lymphocytes in CLL. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID‐19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell‐mediated immunity following mRNA COVID‐19 vaccination (using either BNT162b2 or mRNA‐1273) in short‐term (2‐5 weeks after second dose) and long‐term follow‐up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti‐RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short‐ and long‐term follow‐up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short‐term and 71% in long‐term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS‐CoV‐2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS‐CoV‐2 might be induced by vaccination but do not correlate positively with serological responses. [ABSTRACT FROM AUTHOR]

Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient's own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL. [ABSTRACT FROM AUTHOR]

In recent years significant progress has been made in the clinical management of chronic lymphocytic leukemia (CLL) as well as other B-cell malignancies; targeting proximal B-cell receptor signaling molecules such as Bruton Tyrosine Kinase (BTK) and Phosphoinositide 3-kinase (PI3Kδ) has emerged as a successful treatment strategy. Unfortunately, a proportion of patients are still not cured with available therapeutic options, thus efforts devoted to studying and identifying new potential druggable targets are warranted. B-cell receptor stimulation triggers a complex cascade of signaling events that eventually drives the activation of downstream transcription factors including Nuclear Factor of Activated T cells (NFAT). In this review, we summarize the literature on the expression and function of NFAT family members in CLL where NFAT is not only overexpressed but also constitutively activated; NFAT controls B-cell anergy and targeting this molecule using specific inhibitors impacts on CLL cell viability. Next, we extend our analysis on other mature B-cell lymphomas where a distinct pattern of expression and activation of NFAT is reported. We discuss the therapeutic potential of strategies aimed at targeting NFAT in B-cell malignancies not overlooking the fact that NFAT may play additional roles regulating the inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

CD200, a transmembrane type Ia glycoprotein belonging to the immunoglobulin protein superfamily, is broadly expressed on a wide variety of cell types, such as B lymphocytes, a subset of T lymphocytes, dendritic cells, endothelial and neuronal cells. It delivers immunosuppressive signals through its receptor CD200R, which is expressed on monocytes/myeloid cells and T lymphocytes. Moreover, interaction of CD200 with CD200R has also been reported to play a role in the regulation of tumor immunity. Overexpression of CD200 has been reported in chronic lymphocytic leukemia (CLL) and hairy cell leukemia but not in mantle cell lymphoma, thus helping to better discriminate between these different B cell malignancies with different prognosis. In this review, we focus on the role of CD200 expression in the differential diagnosis of mature B-cell neoplasms and on the prognostic significance of CD200 expression in CLL, where conflicting results have been published so far. Of interest, increasing evidences indicate that anti-CD200 treatment might be therapeutically beneficial for treating CD200-expressing malignancies, such as CLL. [ABSTRACT FROM AUTHOR]