We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The impacts of zanubrutinib on immune cells in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.
- Authors
Zou, Yi‐Xin; Zhu, Hua‐Yuan; Li, Xiao‐Tong; Xia, Yi; Miao, Kou‐Rong; Zhao, Si‐Shu; Wu, Yu‐Jie; Wang, Li; Xu, Wei; Li, Jian‐Yong; Zou, Yi-Xin; Zhu, Hua-Yuan; Li, Xiao-Tong; Miao, Kou-Rong; Zhao, Si-Shu; Wu, Yu-Jie; Li, Jian-Yong
- Abstract
Ibrutinib, a first-generation Bruton's tyrosine kinase (BTK) inhibitor, could improve immunity of relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients. Whether zanubrutinib, a second-generation selective BTK inhibitor, has similar effects as ibrutinib remains to be determined. Dynamics of number and immunophenotype of immune cells during zanubrutinib treatment in 25 R/R CLL/SLL patients were examined by flow cytometry and blood routine tests. The expression intensity of programmed death-1 (PD-1) on total CD4+ (P < .01), total CD8+ (P < .01), and T helper cells (P < .05) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on total CD4+ (P = .010) and regulatory T cells (P < .05) reduced after treatment. There were significant differences in expression intensity of CD19 (P < .01), C-X-C chemokine receptor type 5 (CXCR5) (P < .01), and CD49d (P < .05) on B cells before and after treatment. Downregulation of PD-1 on T cells and CXCR5 and CD19 on B cells were observed in nearly all patients after zanubrutinib treatment. Programmed death-ligand 1 expression downregulated, especially in the female, CLL, normal spleen, normal β2-macroglobulin (β2-MG) and abnormal lactate dehydrogenase (LDH) subgroups, and CTLA-4 expression on CD4+ T cells tended to decrease in the male, old, CLL, splenomegaly, abnormal β2-MG, normal LDH, IGHV-mutated and wild-type tumor protein 53 subgroups after zanubrutinib treatment. These findings suggest that zanubrutinib can regulate immunity primarily by improving T cell exhaustion, inhibiting suppressor cells and disrupting CLL cells migration through downregulation of adhesion/homing receptors. Furthermore, favorable changes in cell number and immunophenotype were preferably observed in patients without adverse prognostic factors.
- Subjects
CHRONIC lymphocytic leukemia; T helper cells; SUPPRESSOR cells; B cells; CHEMOKINE receptors
- Publication
Hematological Oncology, 2019, Vol 37, Issue 4, p392
- ISSN
0278-0232
- Publication type
journal article
- DOI
10.1002/hon.2667