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Cited by 304Immunotherapy and Immune ResponsesCancer Immunotherapy and BiomarkersT-cell and B-cell Immunology

Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy

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Rosato, Pamela C., Wijeyesinghe, Sathi, Stolley, J. Michael, Nelson, Christine E., Davis, Rachel L., Manlove, Luke S., Pennell, Christopher A., Blazar, Bruce R. +4 more·2019·Nature Communications
DOI 10.1038/s41467-019-08534-1PMC PMC6362136
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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.

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References 32 · Cited by 304

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Authors
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.
Affiliations
University of Minnesota (US)
Corresponding author
Masopust, David
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-02-04
Volume
10
Issue
1
Pages
567-567
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-08534-1
PMC
PMC6362136
OpenAlex
W2914458679
Cited by
304
References
32
Citations by year
2026: 35 · 2025: 40 · 2024: 45 · 2023: 48 · 2022: 40 · 2021: 44 · 2020: 39 · 2019: 13
FWCI
13.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Scholar Commons (University of South Carolina) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Cancer Research Institute
  • University of Minnesota
  • Dr. Ralph and Marian Falk Medical Research Trust
  • National Heart, Lung, and Blood Institute (R01HL056067)
  • National Cancer Institute (P30CA077598, P01CA065493)
  • National Institute of Allergy and Infectious Diseases (T32AI007313)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F30DK114942)
  • National Institute of Neurological Disorders and Stroke (R01NS097649)
  • National Institute of Dental and Craniofacial Research (T90DE022732)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
cancer immunotherapy, antitumor immunity, CD8+ T cells, immunosuppressive tumor microenvironment, checkpoint blockade, dendritic cells, natural killer cells, antigen presentation
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antigens, Neoplasm, Child, Female, Humans, Immunotherapy, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Middle Aged, Neoplasms, T-Lymphocytes, Cytotoxic, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Mice, Young Adult, Tumor Microenvironment

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