Chronic lymphocytic leukaemia: the role of T cells in a B cell disease

Abstract

Summary Chronic lymphocytic leukaemia (CLL) has long been thought to be an immunosuppressive disease and abnormalities in T‐cell subset distribution and function have been observed in many studies. However, the role of T cells (if any) in disease progression remains unclear and has not been directly studied. This has changed with the advent of new therapies, such as chimeric antigen receptor‐T cells, which actively use retargeted patient‐derived T cells as “living drugs” for CLL. However complete responses are relatively low (~26%) and recent studies have suggested the differentiation status of patient T cells before therapy may influence efficacy. Non‐chemotherapeutic drugs, such as idelalisib and ibrutinib, also have an impact on T cell populations in CLL patients. This review will highlight what is known about T cells in CLL during disease progression and after treatment, and discuss the prospects of using T cells as predictive biomarkers for immune status and response to therapy.

Increased frequency of CD4+PD‐1+HLA‐DR+ T cells is associated with disease progression in CLL

“…The results raise the possibility that phenotypic monitoring of T‐cell subsets could identify patients who might benefit from early intervention and could also be used alongside other clinical parameters for post‐therapy monitoring. This might be particularly relevant to therapies involving BTK/PI3K inhibitors or venetoclax for which the long‐term effects on T‐cell immunity are unknown (Man & Henley, ).…”

Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia

“…dendritic cells (DC) and macrophages] lineage, contribute to the ineffective triggering and maintenance of T-cell responses, as well as to their suboptimal cytotoxic activity. In the context of the adaptive immune response, several aberrations of the T-cell compartment, ranging from phenotypical changes to functional impairment, have been described [as reviewed in (24)(25)(26)]. Besides cellular components, significant alterations of the humoral response also contribute to the tumor immune escape in CLL (5).…”

“…T lymphocytes have a fundamental role in tumor immunesurveillance. In the context of adaptive immune response, CD4+ Th cells are the main actors in antigen recognition, activation of humoral response, cytokine production, and coordination of CD8+ cytotoxic T lymphocyte response [as reviewed in (25,26)]. Overall, circulating CD4+ and CD8+ T lymphocytes are increased in patients with CLL (78)(79)(80).…”

Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia

“…Conventional T Cells T lymphocytes play a pivotal role in tumor immune-surveillance and immune response to infections. CD4+ T helper lymphocytes are the main coordinator of immune response via both cell-to-cell interactions and cytokine production, activating B lymphocytes and CD8+ cytotoxic T lymphocytes [reviewed in [2,3]]. In patients affected by CLL, CD4+ and CD8+ T lymphocyte numbers are increased [4][5][6][7], and several studies have explored a possible prognostic impact of conventional T-cell counts in this disease.…”