Expanded CD16⁺CD56⁺Granzyme B⁺ NK like CD8⁺ T cells an off target effect of bruton's tyrosine kinase inhibitors in Waldenstrom macroglobulinemia.

ABSTRACT: Bruton's tyrosine kinase inhibitors (BTKi), widely used in Waldenström macroglobulinemia (WM), are known to impair B cell function, but their broader immunological effects remain unclear. We investigated the T cell compartment in patients with WM receiving BTKi, including those who underwent a supervised treatment pause before a third COVID-19 mRNA vaccine dose, as well as treatment naïve controls. Using flow cytometry, antigen-specific T cell assays, and single-cell RNA sequencing, we found that BTKi-treated patients exhibited a reduction in naïve T cells, enrichment of terminal effector CD8⁺ T_emra cells, and lower PD-1 expression. Despite poor vaccine-induced RBD-specific memory B cells, CD4⁺ and CD8⁺ T cell responses to SARS-CoV-2 remained detectable, with enhanced CD8⁺ respo

SUBMITTER: Hastak P 

PROVIDER: S-EPMC12497874 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature