The effect of ibrutinib on neutrophil and γδ T cell functions.

Ibrutinib is a BTK/ITK inhibitor with efficacy for the treatment of various lymphoid cancers, including CLL. Considering that innate and adaptative immune defects are a dominant feature of CLL patients, we evaluated whether in vitro ibrutinib affects the survival and function of neutrophils and γδ T cells, key players of the early immune response against microbes. Neutrophils and γδ T cells were obtained from peripheral blood of healthy donors and CLL patients. We found that ibrutinib reduces the production of reactive oxygen species (ROS) and bacteria killing capacity, and slightly impairs neutrophil extracellular traps (NETs) production without affecting bacteria-uptake and CD62L-downregulation induced by fMLP or aggregated IgG. In addition, ibrutinib reduces γδ T cell activation and CD107a degranulation induced by phosphoantigens or anti-CD3. These findings are in agreement with previous data suggesting that ibrutinib interferes with the protective immune response to pathogens, particularly Mycobacteria and Aspergillus.