Effect of the BTK inhibitor ibrutinib on macrophage- and γδ T cell-mediated response against Mycobacterium tuberculosis

COLADO, ANA; GENOULA, MELANIE; COUGOULE, CÉLINE; MARÍN FRANCO, JOSÉ L.; ALMEJÚN, MARÍA B.; RISNIK, DENISE; KVIATCOVSKY, DENISE; PODAZA, ENRIQUE; ELÍAS, ESTEBAN E.; FUENTES, FEDERICO; MARIDONNEAU-PARINI, ISABELLE; BEZARES, FERNANDO R.; FERNANDEZ GRECCO, HORACIO; CABREJO, MARÍA; JANCIC, CAROLINA; SASIAIN, MARÍA DEL CARMEN; GIORDANO, MIRTA; GAMBERALE, ROMINA; BALBOA, LUCIANA; BORGE, MERCEDES

Blood Cancer Journal

Nature Publishing Group

Año: 2018 vol. 8

The Bruton?s tyrosine kinase (BTK) inhibitor ibrutinib is approved by the Food and Drug Administration for its use as first-line treatment in chronic lymphocytic leukemia(CLL). Despite its efficacy, patients treated with ibrutinibrarely achieve complete responses and usually remainunder treatment until progression. Considering theinherent high susceptibility of CLL patients to infections,a better understanding of ibrutinib effects on the immune system might help to estimate the risk of infectiouscomplications on treated patients. Besides its effects on leukemic B cells, ibrutinib also affects functions on T cells, natural killer cells, and macrophages. Given the relevance of macrophages in Mtb immune response, we here evaluated the in vitro effects of ibrutinib on this cell compartment.Additionally, we studied its effects on γδ T cells, another innate immune component reported to be involved in Mtb response.