Tissue-Resident Memory Cells in Pediatric High-Grade Gliomas

Pediatric Cancers

Anusha Preethi Ganesan (Rady)

P. Vijayanand (MCC/LJI)

High-grade gliomas (pHGG) are the most common brain tumors in children and carry poor prognosis, hence there is significant unmet need for improved treatment. Immunotherapy is rapidly emerging as a promising new treatment modality for cancer with durable remission and lesser toxicity than those associated with conventional therapies. Our prior research in pediatric brain tumors has revealed that pHGG are specifically infiltrated by a distinct subset of CD8+ T cells called tissue-resident memory (TRM) cells, contrary to the general view that the brain is immunologically silent. TRM cells are critical players in anti-tumor immunity and hence understanding how these cells function and how they are generated within pHGG is of great importance. The primary aims of this project are: 1) To elucidate the functional significance of CD8+ tissue-resident memory cells in anti-tumor immune responses in pHGG; and 2) To Identify molecular mechanisms driving differentiation and function of HGG-infiltrating CD8+ TRM cells. We will perform in vivo studies in preclinical glioma models by deleting or transferring TRM cells and evaluate the resulting impact on glioma growth. We will utilize cutting- edge molecular tools to assess the factors that promote the generation and function of TRM cells within pHGG. The results from this study will reveal novel molecular pathways to bolster CD8+ TRM cells to promote anti- tumor immunity in pHGG. the which will pave the way for clinical translation in children with pHGG, for whom there are otherwise limited therapeutic options.