Functional virus-specific memory T cells survey glioblastoma

Jianfang Ning; Noah V Gavil; Shaoping Wu; Sathi P Wijeyesinghe; Eyob Weyu; Jun Ma; Ming Li; Florina Nicoleta Grigore; Sanjay Dhawan; Alexander Skorput; Shawn C. Musial; Clark C. Chen; David Masopust; Pamela Rosato

doi:10.1007/s00262-021-03125-w

Functional virus-specific memory T cells survey glioblastoma

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

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	1863-1875
Number of pages	13
Journal	Cancer Immunology, Immunotherapy
Volume	71
Issue number	8
DOIs	https://doi.org/10.1007/s00262-021-03125-w
State	Published - Aug 2022

Bibliographical note

Funding 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.

Funding Information:
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.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Glioblastoma
Memory CD8 + T cell

Publisher link

10.1007/s00262-021-03125-w

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title = "Functional virus-specific memory 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 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.",

keywords = "Glioblastoma, Memory CD8 + T cell",

author = "Jianfang Ning and Gavil, \{Noah V\} and Shaoping Wu and Wijeyesinghe, \{Sathi P\} and Eyob Weyu and Jun Ma and Ming Li and Grigore, \{Florina Nicoleta\} and Sanjay Dhawan and Alexander Skorput and Musial, \{Shawn C.\} and Chen, \{Clark C.\} and David Masopust and Pamela Rosato",

note = "Funding 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

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month = aug,

doi = "10.1007/s00262-021-03125-w",

language = "English (US)",

volume = "71",

pages = "1863--1875",

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AU - Ning, Jianfang

AU - Gavil, Noah V

AU - Wu, Shaoping

AU - Wijeyesinghe, Sathi P

AU - Weyu, Eyob

AU - Ma, Jun

AU - Li, Ming

AU - Grigore, Florina Nicoleta

AU - Dhawan, Sanjay

AU - Skorput, Alexander

AU - Musial, Shawn C.

AU - Chen, Clark C.

AU - Masopust, David

AU - Rosato, Pamela

N1 - Funding 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. Funding Information: 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. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2022/8

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N2 - 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.

AB - 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.

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IS - 8

ER -

Functional virus-specific memory T cells survey glioblastoma

Abstract

Bibliographical note

UN SDGs

Keywords

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