The role of BTK inhibitors on the tumor microenvironment in CLL

The CLL disease course is heterogeneous with many patients never requiring treatment and some having very aggressive rapid onset disease.Innate and adaptive immune compensatory mechanisms driven by malignant cells often lead to clonal proliferation, migration and resistance to treatment in CLL. Cell-to-cell interactions occurring within the tumor Micro-environment (TME) can impact greatly on the course of the disease as well as contribute to the variable spread of CLL cells, known as spatial heterogeneity. Following evidence showing the expression of BTK on many hematopoietic cells (an exception beting T lymphocytes) has given rise to the idea that inhibition of BTK with BTK inhibitors (BTKi) such as ibrutinib can help treat CLL.As BTK has a wide variation of expression among cells the use of BTKi has been shown to not only control CLL clones but also redistribute the balance of humoral immunity back toward those of healthy control. n this review article we look at role of BTK in the pathogenesis of CLL, the use of BTKi and their effect on humoral immunity.