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Therapeutic activation of virus-specific resident memory T cells within the glioblastoma microenvironment

By Jianfang Ning, Noah Gavil, Shaoping Wu, Sathi Wijeyesinghe, Eyob Weyu, Jun Ma, Ming Li, Florina-Nicoleta Grigore, Sanjay Dhawan, Alexander G.J. Skorput, Shawn C Musial, Clark C Chen, David Masopust, Pamela C Rosato

Posted 06 Sep 2021
bioRxiv DOI: 10.1101/2021.09.06.458939

Glioblastoma multiforme (GBM) is among the most aggressive, treatment resistant cancers, and despite standard of care surgery, radiation and chemotherapy, is invariably fatal. GBM is marked by local and systemic immunosuppression, contributing to resistance to existing immunotherapies that have had success in other tumor types. Memory T cells specific for previous infections reside in tissues throughout the host and these tissue resident memory T cells (TRM) are capable of rapid and potent immune activation. Here, we show that virus-specific memory CD8+ T cells expressing tissue resident markers populate mouse and human glioblastoma microenvironment. Reactivating virus-specific TRM through intra-tumoral delivery of adjuvant-free virus-derived peptide triggered local immune activation. This delivery translated to anti-neoplastic effects, which improved survival in a murine glioblastoma model. Our results indicate that virus-specific TRM are a significant part of the glioblastoma immune microenvironment and can be leveraged to promote anti-tumoral immunity.

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