Characterization of the Xeno-GVHD Response Generated by Lung Cancer Patient PBMCs in NSG-SGM3 Mice

Abstract Humanized mouse models based on PBMC transplants have become a critical preclinical platform for NSCLC investigation. However, the emergence of xeno-GVHD poses challenges that need clarification. In this study, we explore clinical and molecular aspects of xeno-GVHD induced by NSCLC patient PBMCs compared to healthy donors in the novel NSG-SGM3 mice. PBMCs from NSCLC patients and healthy donors were injected into NSG-SGM3 mice and monitored for eight weeks to assess xeno-GVHD onset and progression. Clinical signs, such as weight loss, anemia, and low platelet count, appeared early, with severe symptoms more prevalent in healthy donor models. Flow cytometry revealed a dominance of CD8 T cells, primarily effector T-cells, in peripheral blood, while organ examination highlighted a prevalence of CD4 effector T cells. Our findings demonstrate that xeno-GVHD from NSCLC patients is delayed and less severe than healthy controls in the NSG-SGM3 mice model, likely due to treatment history affecting patients' PBMCs' functional state. Our data contribute essential knowledge for advancing PBMCs humanized models in NSCLC treatment studies and may offer a novel tool for immune system assessment.