(545) Characterization of the brain immune microenvironment in healthy mice and a human infant with AT/RT

Introduction/Rationale: Atypical Teratoid/Rhabdoid Tumors (AT/RT) are devastating brain tumors with high mortality. Due to rare occurrence in infants, lack of understanding of brain microenvironment prior to treatment, and majority of studied tissues being from heavily treated individuals, the overall immune response to these tumors are unknown.

Methods: We obtained autopsy brain tissue and blood within 12 hours of death and performed high parameter flow cytometry.

Results: We reliably isolated immune cells from brain and blood (PBMC: 92%, brain: 54.4% viable cells). Unlike brain tissue isolated from newly-diagnosed adult glioblastoma, this 8-week-old AT/RT patient had significant infiltration of activated PD1+ CD8 T cells in the brain. While significant numbers of CD8 T cells with high expression of proliferation marker (Ki67) and activation markers (PD1, CD69) were found, no evidence of exhaustion was seen. Few Tregs and suppressive myeloid cells were in the brain. This immune phenotype is conducive to immunotherapies. In the matched blood, few T cells were found, which reflects infant lymphopenia. To elucidate immune microenvironment of a healthy brain in infancy, we performed flow cytometry on 2- and 4-day old mice, an age developmentally similar to 8-week-old human infants. We found various immune cells including proliferating T cells in brains, indicating a potential role in the developing brain.

Conclusion: Understanding the state of immunity in brains of infants will pave the way for design of effective immunotherapies.