Immune resilience after pediatric cancer treatment 4311

Abstract Description Advances in pediatric cancer treatment have increased the survival rate to 85%, yet survivors remain at higher risk for developing severe chronic diseases and infection-related mortality, likely due to immune dysfunction - a largely understudied area. Emerging hypothesis suggests that immune health is a dynamic manifestation of the basal immune state and adaptive immune memory. Cancer and its treatment disrupt this balance, and it is unclear if survivors’ immune system returns to its basal state or reconstitutes to a new immune state post treatment. To address this, SOMAscan serum measurements were conducted on survivors from the St. Jude Lifetime cohort diagnosed with Acute Lymphoblastic Leukemia (ALL, n = 75) or Hodgkin’s Lymphoma (HL, n = 102), including a mix of subjects who did or did not develop frailty, and compared to age-matched healthy control (n = 78). Preliminary data show non-frail HL individuals have elevated inflammatory markers (IL-3, IL-21R, IL-1RA, CRP) and reduced immune factors (IL-9, G-CSF, serotransferrin, IL-23, PDGF-A/B), along with changes in DNAJB9 and NELL-1. Non-frail ALL survivors show unique markers (TGF-beta-1, PD-L1, GM-CSF) along with shared markers with HL survivors (NELL-1, PDGF-A, IL-9, IL-3, IL-21R, IL-1RA), indicating a common biological response. Further analyses, including frailty comparisons, longitudinal T cell profiling, and single-cell sequencing of T cells, are underway to deepen understanding of immune resilience post-treatment. Funding Sources Supported by U01 CA195547; P30 CA021765. Topic Categories Immune Mechanisms of Human Disease (HUM)