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 (T_RM) 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 T_RM 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 T_RM are a significant part of the glioblastoma immune microenvironment and can be leveraged to promote anti-tumoral immunity.

中文翻译：

---

胶质母细胞瘤微环境中病毒特异性常驻记忆 T 细胞的治疗性激活

多形性胶质母细胞瘤 (GBM) 是最具侵袭性、最难治疗的癌症之一，尽管有标准的手术、放疗和化疗，但它总是致命的。GBM 的特点是局部和全身免疫抑制，导致对已在其他肿瘤类型中取得成功的现有免疫疗法产生耐药性。对先前感染特异的记忆 T 细胞存在于整个宿主的组织中，这些组织驻留记忆 T 细胞 ( _TRM ) 能够快速有效地激活免疫。在这里，我们展示了表达组织驻留标记的病毒特异性记忆 CD8+ T 细胞填充了小鼠和人类胶质母细胞瘤的微环境。重新激活病毒特异性_TRM通过肿瘤内递送无佐剂的病毒衍生肽触发局部免疫激活。这种传递转化为抗肿瘤作用，从而提高了小鼠胶质母细胞瘤模型的存活率。我们的结果表明，病毒特异性_TRM是胶质母细胞瘤免疫微环境的重要组成部分，可用于促进抗肿瘤免疫。