Second generation BTK inhibitors impair the anti-fungal response of macrophages and neutrophils from CLL patients

COLADO, ANA; MARÍN FRANCO, JOSÉ LUIS; ELÍAS, ESTEBAN ENRIQUE; AMONDARAIN, MIKELE; RUBIO, MARICEF VERGARA; MARTÍNEZ, VALERIA SARAPURA; CORDINI, GREGORIO; FUENTES, FEDERICO; BALBOA, LUCIANA; FERNÁNDEZ GRECCO, HORACIO; PAVLOVSKY, MIGUEL; BEZARES, FERNANDO; MORANDE, PABLO; GIORDANO, MIRTA; GAMBERALE, ROMINA; BORGE, MERCEDES

AMERICAN JOURNAL OF HEMATOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2020

0361-8609

Bruton Tyrosine Kinase (BTK) is a Tec family non-receptor protein kinase essential for the signaling through the B cell receptor (BCR). Signaling through the BCR plays a key role in CLL pathogenesis and progression. In fact, several alterations in the BCR signaling pathway were described on leukemic cells from CLL patients including over expression and constitutive phosphorilation of BTK. If second generation BTKi affect macrophage and neutrophil responses to fungi was not evaluated yet. Our aim was to compare the effect of acalabrutinib, spebrutinib, and ibrutinib on macrophage and neutrophil functions and on the cellular mediated mechanisms of action of anti-CD20 antibodies used for CLL treatment. Our results show that BTKi have inhibitory effects on key innate immune cells. Second generation BTKi may have fewer effects on anti-CD20 mechanism of actions, and so, can be considered as better partners for combinatory treatment. On the other hand, second generation BTKi, particularly acalabrutinib, showed similar effect on macrophages and neutrophils to that of ibrutinib, that may impact on the anti-microbial immune response in vivo and should be taken into account especially in the presence of other factors that weaken the immune system.