CD40L and IL-4 suppress NK cell-mediated antibody-dependent cellular cytotoxicity through the HLA-E:NKG2A axis.

ABSTRACT:

Background

Anti-CD20 antibodies are first-line treatments for B cell malignancies. Natural killer (NK) cells are important mediators of anti-CD20 antibody efficacy in humans through antibody-dependent cellular cytotoxicity (ADCC). In B cell malignancies, the lymph nodes are a critical site of pathology and the T cell-derived signals CD40L and IL-4 within the lymph node microenvironment can mediate tumour proliferation, survival and resistance to pro-apoptotic therapy. CD40L and IL-4 have recently been shown to inhibit NK cell activation against chronic lymphocytic leukaemia (CLL) cells via the HLA-E:NKG2A immune checkpoint axis. However, the effect of these signals on NK cell-mediated ADCC of malignant B cells is unclear.

Methods

Using a combination of clinical samples, muri

SUBMITTER: Graham LV 

PROVIDER: S-EPMC12448733 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature