%0 Journal Article
%T NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity.
%A Aryee KE
%A Shultz LD
%A Burzenski LM
%A Greiner DL
%A Brehm MA
%J J Leukoc Biol
%V 113
%N 5
%D 05 2023 2
%M 36801998
%F 6.011
%R 10.1093/jleuko/qiac020
%X Agents that induce inflammation have been used since the 18th century for the treatment of cancer. The inflammation induced by agents such as Toll-like receptor agonists is thought to stimulate tumor-specific immunity in patients and augment control of tumor burden. While NOD-scid IL2rγnull mice lack murine adaptive immunity (T cells and B cells), these mice maintain a residual murine innate immune system that responds to Toll-like receptor agonists. Here we describe a novel NOD-scid IL2rγnull mouse lacking murine TLR4 that fails to respond to lipopolysaccharide. NSG-Tlr4null mice support human immune system engraftment and enable the study of human-specific responses to TLR4 agonists in the absence of the confounding effects of a murine response. Our data demonstrate that specific stimulation of TLR4 activates human innate immune systems and delays the growth kinetics of a human patient-derived xenograft melanoma tumor.