Pediatric brain tumor patients display altered immune activation and reduced lymphopoiesis at the onset of disease

Marco Rosichini; Giada Del Baldo; Carmen Dolores De Luca; Francesca Benini; Shirley Genah; Maria Vinci; Alfredo Cerimele; Marianna Coccetti; Sara Flamini; Rita Carsetti; Antonella Cacchione; Andrea Carai; Angela Mastronuzzi; Franco Locatelli; Enrico Velardi

doi:10.1038/s41698-024-00755-y

Pediatric brain tumor patients display altered immune activation and reduced lymphopoiesis at the onset of disease

NPJ Precis Oncol. 2024 Nov 20;8(1):269. doi: 10.1038/s41698-024-00755-y.

Authors

Marco Rosichini^#^{1

2}, Giada Del Baldo^#^{1

3}, Carmen Dolores De Luca¹, Francesca Benini¹, Shirley Genah¹, Maria Vinci¹, Alfredo Cerimele¹, Marianna Coccetti⁴, Sara Flamini¹, Rita Carsetti⁵, Antonella Cacchione¹, Andrea Carai⁶, Angela Mastronuzzi^#¹, Franco Locatelli^#^{1

7}, Enrico Velardi^#⁸

Affiliations

¹ Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
² Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
³ Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
⁴ Research Core Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁵ B cell unit Research Area of Immunology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ Department of Neurosciences, Neurosurgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁷ Catholic University of the Sacred Heart, Rome, Italy.
⁸ Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. [email protected].

^# Contributed equally.

Abstract

Optimal immune function is crucial in preventing cancer development and growth and for the success of anti-cancer therapies. Here, we characterized the peripheral immunological status of 83 steroids-naïve pediatric patients with central nervous system neoplasia at the disease onset. Tumors were classified into low-grade gliomas (LGG), high-grade gliomas (HGG), medulloblastoma, and other tumors. We revealed that glioma patients showed an altered lymphocyte pool. T-cells of HGG patients shifted from naïve to effector memory phenotype. LGG patients exhibited T-cell central memory expansion and higher T-cell activation. Interestingly, HGG patients displayed reduced thymic function. Furthermore, LGG and HGG patients showed reduced activated B-cells and suboptimal B-cell formation. Our data demonstrate that glioma patients have reduced lymphopoiesis at the disease onset, which could contribute to the systemic lymphopenia characterizing these patients. This study offers novel insights into the immunological status of brain tumor patients which may help in designing more effective treatments.