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 are capable of rapid and potent immune activation. Here, we show that virus-specific memory CD8 + T cells expressing tissue-resident markers populate the mouse and human glioblastoma microenvironment. Reactivating virus-specific memory T cells through intratumoral delivery of adjuvant-free virus-derived peptide triggered local immune activation. This delivery translated to antineoplastic effects, which improved survival in a murine glioblastoma model. Our results indicate that virus-specific memory T cells are a significant part of the glioblastoma immune microenvironment and may be leveraged to promote anti-tumoral immunity.
Bibliographical noteFunding Information:
This work was supported by a UMN SPORE Program Project Planning grant (DM, CCC), NCI 1R01CA238439 (DM), Humor to Fight the Tumor Foundation (JN), and support from the Norris Cotton Cancer Center, NCI 5P30CA023108-42 (PR). The authors have no relevant financial or non-financial interests to disclose. The datasets generated during and/or analyzed during the current study are available from the corresponding author on request.
The authors thank Dr. Ryan Langlois for PR8-gp33, the NIH Tetramer Facility for HLA-A*02:01 heavy chain plasmid, the Minnesota Supercomputing Institute for assistance with RNA sequencing, and University of Minnesota (UMN) BioNet for assistance with human samples.
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
- Memory CD8 + T cell
PubMed: MeSH publication types
- Journal Article