Document Type
Article
Subject Area(s)
Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antigens, Neoplasm (immunology); CD8-Positive T-Lymphocytes (metabolism); Cell Line, Tumor; Child; Female; Humans; Immunotherapy (methods); Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Middle Aged; Neoplasms (immunology, therapy); T-Lymphocytes, Cytotoxic (immunology, metabolism, virology); Tumor Microenvironment (immunology, physiology); Young Adult
Abstract
The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune system. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles observed in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy.
Digital Object Identifier (DOI)
Publication Info
Published in Nature Communications, Volume 10, Issue 567, 2019.
Rights
© The Author(s) 2019 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
APA Citation
Rosato, P. C., Wijeyesinghe, S., Stolley, J. M., Nelson, C. E., Davis, R. L., Manlove, L. S., Pennell, C. A., Blazar, B. R., Chen, C. C., Geller, M. A., Vezys, V., & Masopust, D. (2019). Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nature Communications, 10(567). https://doi.org/10.1038/s41467-019-08534-1