BIOM-04. ALTERED IMMUNE ACTIVATION AND REDUCED LYMPHOPOIESIS IN TREATMENT NAÏVE PEDIATRIC BRAIN TUMOUR PATIENTS

Abstract

Abstract Pediatric central nervous system (CNS) tumors are the most common solid tumor in children. Despite improvements in diagnostic and therapeutic approaches over time, treatment effectiveness remains unsatisfactory. Optimal immune function is critical to protect against development and dissemination of cancer and to offer the ideal conditions for the success of anticancer treatment. Here we analyzed the peripheral immunological features of patients affected by pediatric brain tumors, the process of de novo T- and B-cell development and its association with the lymphopenia often observed in these patients. Eighty-six steroids-naïve pediatric patients with CNS tumors at the onset of the disease were included in the study. Brain tumors were classified into low-grade gliomas (LGG: n=44, 51%), pediatric-type diffuse high-grade gliomas (pHGG: n=16, 19%), medulloblastoma (n =9, 10%), and other CNS tumors (n =17, 20%). Patient’s peripheral immunological status was analyzed by flow-cytometry and by evaluating T-cell receptor excision circles (TRECs) and kappa-deleting excision circles (KREC) to quantify T- and B-cell neogenesis. Although all patients showed tendencies towards low lymphocyte counts, this effect was particularly evident in pHGG patients. T-cells of pHGG patients displayed a shift from naïve to effector memory phenotype compared to age-matched controls. On the other hand, LGG patients were characterized by an expansion of the T-central memory pool and higher expression of T-cell activation markers. Both patient cohorts exhibited decreased frequency of B-cells with activated phenotype. Interestingly, pHGG patients exhibited reduced thymic function as revealed by reduced levels of the recent thymic emigrant population and TRECs. In addition, LGG and pHGG patients were characterized by lower KREC values, suggesting suboptimal B-cell formation. At diagnosis, pediatric patients with brain tumor show alterations in their immunological status and reduced thymic and medullary lymphopoiesis, particularly pronounced in pHGG, which may contribute to explain the systemic lymphopenia characterizing these patients.