title: Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia.
abstract: Ibrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimulus in CD14+cells, improving levels of phospho-Erk1/2 and antigen presentation. Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression. Our data suggest the impact of BTK inhibition along with immunomodulation on the innate immune response and a switch to the specific adaptive immune response, which might help to decrease infectious complications. The potential effect of ibrutinib on CLL patient outcomes is worthy of further study, because infections could be reduced with the use of ibrutinib.
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, Madrid, Spain; Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain; Center for Biomedical Research Network, CIBEres, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cubillos-Zapata
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, Madrid, Spain; Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Avendaño-Ortiz
authors.affiliation: Lymphoma Unit, Oncohealth Institute and Health Research Institute IIS-FJS, Autonomous University of Madrid, Madrid, Spain; START Madrid FJD, Phase 1 Clinical Trials Unit, Foundation Jiménez Díaz University Hospital, Madrid, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Córdoba
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, Madrid, Spain; Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain; Center for Biomedical Research Network, CIBEres, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Jiménez
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, Madrid, Spain; Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain; Center for Biomedical Research Network, CIBEres, Madrid, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Toledano
authors.affiliation: Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain; Laboratory of Immunogenetics of Diseases, Madrid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Pérez de Diego
authors.affiliation: Tumor Immunology Laboratory, IdiPAZ, Madrid, Spain; Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain; Center for Biomedical Research Network, CIBEres, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
keywords: CLL patients; ibrutinib treatment; immune response