{Reference Type}: Journal Article
{Title}: NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity.
{Author}: Aryee KE;Shultz LD;Burzenski LM;Greiner DL;Brehm MA;
{Journal}: J Leukoc Biol
{Volume}: 113
{Issue}: 5
{Year}: 05 2023 2
{Factor}: 6.011
{DOI}: 10.1093/jleuko/qiac020
{Abstract}: 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.