A Neonatal Intravenous Transplant Model for Assessment of Early-Life Immune Activities Against Cancer Cells

More than half of all pediatric cancers are initiated in utero, with progression towards overt disease continuing through the neonatal period. While immunotherapies now offer new treatment options for many children with cancer, how early-life immunity influences cancer progression and therapy response remains incompletely understood. Addressing this gap will require evaluation of therapeutic interventions during the neonatal period, when immune responses differ fundamentally from those in later childhood and adulthood. Here, we describe a neonatal transplantation model that integrates with bioluminescent in vivo imaging to investigate the impact of early-life immune modulation on pediatric cancers. Temporal vein injection of luciferase-tagged cells derived from two in utero-initiated cancers achieved reproducible tumour engraftment in 1-2-day-old syngeneic recipients, with no procedure-related mortality and high procedural success as confirmed by bioluminescent imaging. Using infection-driven immune modulation as an experimental variable, we then show that intraperitoneal infection with murine cytomegalovirus five days after transplantation results in a marked reduction in the burden of acute lymphoblastic leukemia (ALL), but not neuroblastoma (NB). This platform enables the study of cancer-specific differences in response to early-life immune modulation and underscores the importance of tumor context when modeling immune-cancer interactions in early life. Collectively, this methodology provides a versatile and highly reproducible platform for interrogating neonatal immune mechanisms relevant to cancer immunosurveillance, infection-driven immune modulation, and therapeutic intervention. Beyond ALL and NB, this approach can be adapted to additional pediatric malignancies and immunomodulatory strategies, supporting mechanistic studies and preclinical evaluation of early-life cancer interventions.