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, Giada Del Baldo Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy Search for other works by this author on: Oxford Academic Marco Rosichini Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Maria Vinci Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Andrea Carai Department of Neurosciences, Neurosurgery Unit, Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Antonella Cacchione Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Carmen Dolores De Luca Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Francesca Benini Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Shirley Genah Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Marianna Concetti Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Angela Mastronuzzi Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic
, Franco Locatelli Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Enrico Velardi Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic
Neuro-Oncology, Volume 26, Issue Supplement_4, June 2024, Page 0, https://doi.org/10.1093/neuonc/noae064.024
Published:
18 June 2024
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Giada Del Baldo, Marco Rosichini, Maria Vinci, Andrea Carai, Antonella Cacchione, Carmen Dolores De Luca, Francesca Benini, Shirley Genah, Marianna Concetti, Angela Mastronuzzi, Franco Locatelli, Enrico Velardi, BIOM-04. ALTERED IMMUNE ACTIVATION AND REDUCED LYMPHOPOIESIS IN TREATMENT NAÏVE PEDIATRIC BRAIN TUMOUR PATIENTS, Neuro-Oncology, Volume 26, Issue Supplement_4, June 2024, Page 0, https://doi.org/10.1093/neuonc/noae064.024
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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.
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© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Issue Section:
Final category: Biological Correlates, Biomarkers
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