Monitor the immune microenvironment and systemic immune effects in pediatric brain tumors the mimic program

INTRODUCTION Dismal outcomes of pediatric high-grade CNS tumors demand new therapeutic strategies. A better understanding of the immune system may contribute to designing better immunotherapies for these children. The MIMIC program (Dutch Trial Registry NL8967) is a prospective observational longitudinal cohort study, conducted in patients with newly diagnosed or relapsed high-grade CNS tumors with the aim of characterizing and quantifying changes in immune parameters at diagnosis and during treatment. METHODS All patients with a newly diagnosed or relapsed high-grade CNS tumor are included after obtaining informed consent. Patient study material is collected longitudinally and includes tumor tissue (TT), Cavitron Ultra Sonic Aspirator (CUSA) material and optional bone marrow aspiration (BM) at diagnosis and relapse. Cerebrospinal fluid (CSF), peripheral blood (PB) and fecal samples (FS) at diagnosis, 3 months, 6 months, 12 months, relapse and additionally collection of CSF and FS at 14 days. Furthermore, FS is collected from patient siblings as a reference. RESULTS The MIMIC program has opened in June 2021 in the Princess Máxima Center, the national pediatric oncology center in the Netherlands, including so far 47 patients (out of ~60 eligible patients annually). More than 400 samples, out of which 46 TT, 34 CUSA, 65 CSF, 14 BM, 143 PB, and 105 FS have been collected. All samples are subject to extensive immunological profiling using 70+ markers flow cytometry panels (PB, TT, CUSA, CSF, BM), (spatial single cell) RNA and protein profiling (TT, CUSA, BM), immunohistochemistry (TT), proteomics (CSF and PB), and 16S rRNA or shotgun metagenomic sequencing (FS). CONCLUSION The MIMIC program demonstrates the feasibility of obtaining various samples for pediatric high-grade CNS tumors. By incorporating multiple technologies in longitudinal samples, the MIMIC program provides insight into the different immune compartments and their relation to the tumor, forming the base for future clinical trials with immunotherapy.