Characterization of the xeno-GVHD response generated by advanced lung cancer patient peripheral blood mononuclear cells in NSG-SGM3 mice

Background: Peripheral blood mononuclear cell (PBMC) humanized mouse models are essential for researching non-small cell lung cancer (NSCLC) treatments. However, these models are prone to xeno-graft versus host disease (xeno-GVHD), hampering their utility and requiring further investigation. This study examined xeno-GVHD responses from PBMCs of advanced-stage NSCLC patients compared to healthy donors (HDs) in a humanized peripheral blood lymphocyte (hu-PBL) model. Methods: PBMCs from NSCLC patients and HDs were injected into immunocompromised NSG-SGM3 mice and monitored for eight weeks. xeno-GVHD progression was assessed through clinical examinations and flow cytometry of human T-cell levels in various tissues. Results: Mice injected with PBMCs from HDs showed xeno-GVHD signs as early as 28 days postinjection, whereas those from NSCLC patients exhibited minimal signs, with only one model showing delayed responses by day 42. Clinical symptoms in mice included weight loss, anemia, low platelet counts, fur changes, and behavioral modifications. Flow cytometry of human PBMCs in mice indicated dominant CD8⁺ effector memory T cells in peripheral blood. In contrast, CD4⁺ effector memory T cells were predominant in the organs, with overall T cell levels lower in NSCLC models. Conclusions: This study demonstrates significant differences in xeno-GVHD progression between advance-stage NSCLC patients and HDs, likely influenced by the patient’s treatment histories. These findings improve our understanding of hu-PBL models for NSCLC research and may inform future treatment studies and strategies.