Investigating the source of viral-specific memory T cells in glioblastoma

Abstract

Abstract Glioblastoma (GBM) is an aggressive primary brain tumor that is invariably fatal. Immunotherapies have largely failed and a better understanding of the unique brain tumor immune environment is needed. Being historically thought of as immune-privileged, immune cell populations within the brain and brain tumors have been understudied. One such population is resident memory T cells (T RM). In healthy and malignant peripheral tissues, T RMcan provide long-term protection against reinfections or cancers, however the role of T RMin the context of the brain and brain tumors is not fully understood. Our lab has discovered that memory T cells specific for common viral infections populate human brain tumors to high frequencies and express markers indicative of tissue residency. We also find these virus-specific memory T cells (vsT M) in mouse models of GBM, despite the absence of infection. Surveillance of tumors by bystander (non-tumor specific) memory T cells is understudied despite their potential to contribute to anti-tumor immunity. Indeed, the source of these cells is unknown; they may originate from circulating memory T cells that infiltrate the tumor, and/or pre-existing T RMthat were in the brain prior to tumor formation. To dissect the origin of vsT Min brain tumors we established mouse models with distinct memory T cell compartments. Preliminary data suggests that pre-established vsT RMin healthy brain are the main contributors to tumor vsT M. Future work will assess if vsT Mare resident within tumors, and extend studies to virus-specific T cell populations in human brain tumors. Our findings will broaden our understanding of GBM immunosurveillance, and provide valuable insights for the development of novel T cell-based immunotherapies. Supported by grants from the Dartmouth Cancer Center