Aidan Gadepalli
Research Mentor: Erika Newman
Mentor Department: Pediatric Surgery, Medicine
Author(s): Aidan Gadepalli, Sahiti Chukkapalli, Keyonna Williams, Anjalika Dandamudi, Ejaz Ahmad, Erika Newman
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 72
Abstract
Maternal nutrition during pregnancy is a key determinant of offspring health, influencing susceptibility to diseases like cancer. Neuroblastoma, a childhood cancer in the nervous system, is highly sensitive to both genetic and early-life environmental factors. While certain oncogenic drivers (like MYCN amplification) are well-characterized, the role of in utero environmental exposures—particularly maternal diet—remains underexplored. This study investigates how a prenatal high-fat diet (HFD) influences neuroblastoma progression and anti-tumor immunity in genetically predisposed offspring. Using the TH-MYCN transgenic mouse model, which develops spontaneous neuroblastoma, pregnant mice were fed either a control diet or an HFD throughout gestation. Offspring were assessed for tumor onset, progression rate, tumor burden, and survival. Immune profiling of the tumor microenvironment was performed to evaluate T cell function and exhaustion status. Offspring exposed to an HFD in utero exhibited significantly earlier tumor onset, accelerated progression, and increased tumor burden compared to controls. These changes were accompanied by reduced overall survival, indicating a more aggressive tumor phenotype. Spleen was enlarged in HFD group mice when compared to controls. Flow cytometric analysis of spleen immune composition revealed a suppressed anti-tumor immune response, particularly among CD4? T cells. These cells displayed elevated expression of exhaustion markers, including PD-1, TIM-3, and LAG-3, alongside reduced proliferation and diminished cytokine production (IL-2, IFN-?). A notable increase in CD4?CD44?CD62L? cells was also observed, suggesting abnormal T cell differentiation or functional impairment. The HFD-exposed mice showed increased immunosuppressive signaling and altered antigen presentation, further supporting a state of immune dysfunction. These results suggest that prenatal HFD exposure induces long-lasting immune alterations that compromise anti-tumor immunity and promote neuroblastoma progression. Prenatal exposure to a high-fat diet accelerates neuroblastoma development and impairs adaptive immunity through the exhaustion and dysfunction of CD4? T cells. These findings for the first time underscore the importance of maternal nutrition in shaping cancer biology and immune competence in offspring. Targeting maternal dietary habits may offer a novel approach to reducing childhood cancer risk.
