Functional virus-specific memory CD8+ T cells survey glioblastoma

Abstract 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...

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Published inThe Journal of immunology (1950) Vol. 208; no. 1_Supplement; pp. 121 - 121.15
Main Authors Rosato, Pamela, Ning, Jianfang, Gavil, Noah Veis, Wu, Shaoping, Wijeyesinghe, Sathi, Weyu, Eyob, Ma, Jun, Li, Ming, Grigore, Florina-Nicoleta, Dhawan, Sanjay, Skorput, Alexander G., Musial, Shawn C, Kleist, Sierra A., Isaacs, Jordan F., Chen, Clark C, Masopust, David
Format Journal Article
LanguageEnglish
Published 01.05.2022
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Abstract Abstract 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, including the brain, 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 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 memory T cells are a significant part of the glioblastoma immune microenvironment and may be leveraged to promote anti-tumoral immunity. Supported by UMN SPORE Program Project Planning grant (DM, CCC), NCI 1R01CA238439 (DM), Humor to Fight the Tumor Foundation (JN), NCI 5P30CA023108-42 (PR)
AbstractList Abstract 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, including the brain, 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 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 memory T cells are a significant part of the glioblastoma immune microenvironment and may be leveraged to promote anti-tumoral immunity. Supported by UMN SPORE Program Project Planning grant (DM, CCC), NCI 1R01CA238439 (DM), Humor to Fight the Tumor Foundation (JN), NCI 5P30CA023108-42 (PR)
Author Wijeyesinghe, Sathi
Li, Ming
Masopust, David
Gavil, Noah Veis
Musial, Shawn C
Ning, Jianfang
Kleist, Sierra A.
Isaacs, Jordan F.
Skorput, Alexander G.
Weyu, Eyob
Grigore, Florina-Nicoleta
Chen, Clark C
Rosato, Pamela
Wu, Shaoping
Ma, Jun
Dhawan, Sanjay
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