Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.

Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous B cell malignancy in which non-malignant T lymphocytes constitute a critical component of the tumor microenvironment and significantly influence disease evolution and the therapeutic response. Growing evidence suggests that CLL-associated T cells not only participate in the antitumor response but also activate signals that promote the development of CLL subclones. Although novel targeted therapies, such as Bruton's tyrosine kinase (BTK) inhibitors, BTK degraders, B-cell lymphoma 2 (BCL-2) inhibitors, T cell engagers, immune checkpoint inhibitors, and adoptive T cell therapy have different mechanisms of action, they affect the T cell compartment in addition to targeting CLL cells. Therefore, in-depth knowledge of the role of T cells in the development and progression of CLL is essential for proper stratification of the benefit-to-risk ratio with regard to immunotherapeutic strategies. This review comprehensively summarizes current knowledge on alterations within the T cell compartment in CLL and discusses the clinical implications, regarding clinical course and response to immunotherapy.