Immunomodulatory effects of imatinib and second-generation tyrosine kinase inhibitors on T cells and dendritic cells: an update.

The discovery of new drugs has occasionally led to a better understanding of biologic processes and unforeseen therapeutic applications. One such example is the new group of tyrosine kinase inhibitors, exemplified by the Bcr-Abl inhibitor imatinib (Glivec). In the last 10 years, these so-called 'small molecules' have started to enter the clinic with the promise of cancer treatments targeted at the underlying molecular changes that are responsible for specific malignant phenotypes. The aim of these small molecules has been to avoid the side-effects of systemic chemotherapies and the high morbidity/mortality risks associated with hematopoietic stem cell transplantation. Concurrently, however, increasing evidence has emerged to indicate that these drugs exert profound immunomodulatory effects on T cells and antigen-presenting cells, such as dendritic cells, which play major roles in immune tumor surveillance and the outcome of hematopoietic stem cell transplantation. Targeted tyrosine kinase inhibitor therapy may thus control cancer cell growth both directly and indirectly by changing the immunologic microenvironment. Furthermore, such molecules might help to unravel the complexities of the human immune system and could find therapeutic application in conditions as diverse as autoimmune diseases and certain infectious processes. In this brief review, we discuss recent developments in this fast evolving field.