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The impacts of zanubrutinib on immune cells in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma
Author(s) -
Zou YiXin,
Zhu HuaYuan,
Li XiaoTong,
Xia Yi,
Miao KouRong,
Zhao SiShu,
Wu YuJie,
Wang Li,
Xu Wei,
Li JianYong
Publication year - 2019
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2667
Subject(s) - ibrutinib , chronic lymphocytic leukemia , cd8 , immune system , immunology , bruton's tyrosine kinase , cancer research , cd38 , biology , medicine , leukemia , tyrosine kinase , receptor , cd34 , stem cell , genetics
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.

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