4.7 Article

Functional virus-specific memory T cells survey glioblastoma

期刊

CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 71, 期 8, 页码 1863-1875

出版社

SPRINGER
DOI: 10.1007/s00262-021-03125-w

关键词

Glioblastoma; Memory CD8+T cell

资金

  1. UMN SPORE Program Project Planning grant
  2. NCI [1R01CA238439]
  3. Humor to Fight the Tumor Foundation
  4. Norris Cotton Cancer Center [NCI 5P30CA023108-42]

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This study reveals the presence of virus-specific memory T cells expressing tissue-resident markers in the immune microenvironment of glioblastoma. Reactivation of these cells through intratumoral delivery of virus-derived peptides leads to local immune activation and antineoplastic effects.
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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