Immune resilience after pediatric cancer treatment 2309878

Abstract

Abstract Introduction Long-term survivors of pediatric cancer remain at increased risk for chronic conditions and infection-related mortality, likely due to persistent immune dysfunction. However, the long-term immune landscape in adult survivors of childhood cancer remains poorly defined. Emerging hypothesis indicates 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 whether survivors’ immune systems return to their basal state or reconstitute to a new immune state post-treatment. Methods To address this, SOMASCAN serum sample measurement was done for cancer survivors who were diagnosed with Acute Lymphoblastic Leukemia (ALL) (n = 75) or Hodgkin’s Lymphoma (HL) (n = 102) from the St. Jude lifetime cohort (SJLIFE), selected based on the progression of clinical outcomes. Samples were profiled for immune and clinical markers and compared to age matched healthy control (HC) (n = 78). Additionally, single-cell sequencing was performed on a subset of individuals diagnosed with ALL (n = 6), HL (n = 6), and HC (n = 6), selected based on chronic disease burden (CDB) and frailty. Older HC samples (n = 3) was included to evaluate the similarity of survivor immune profiles to those of advanced age. Results Preliminary analyses suggest that pediatric survivors exhibit a significantly higher CDB compared to HC, based on regression models adjusted for demographic differences. Frailty independently predicted increased CDB, even after adjusting for age, sex, and race with prefrail/frail patients associated with higher CDB. Distinct protein markers showed associations with CDB in ALL and HL, based on regression-adjusted analyses. Markers included TNF-α, LEG9, Epo and IL-25 in ALL, and CXCL10, CCL3, CCL1 and IL-1β in HL. Conclusion These data highlight immune alterations in childhood cancer survivors. Ongoing analyses will aim to further characterize immune features following cancer treatment. Funding Source n/a Topic Categories Immune Mechanisms of Human Disease (HUM)