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Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019), Nature Communications
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.<br />The immunosuppressive tumor environment and the lack of functional anti-tumor immunity are major limiting factors in immunotherapy. Here the authors show that human and mouse tumors are infiltrated by virus-specific memory T cells, which can be harnessed by viral peptides to induce local and systemic anti-tumor immunity and synergize with checkpoint blockade.
- Subjects :
- Male
0301 basic medicine
medicine.medical_treatment
General Physics and Astronomy
02 engineering and technology
CD8-Positive T-Lymphocytes
Mice
Cancer immunotherapy
Neoplasms
Tumor Microenvironment
Cytotoxic T cell
Child
lcsh:Science
Aged, 80 and over
Multidisciplinary
Middle Aged
021001 nanoscience & nanotechnology
Acquired immune system
Female
Immunotherapy
0210 nano-technology
Adult
Adolescent
Science
Antigen presentation
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Young Adult
03 medical and health sciences
Antigen
Antigens, Neoplasm
Cell Line, Tumor
medicine
Animals
Humans
Aged
Tumor microenvironment
General Chemistry
biochemical phenomena, metabolism, and nutrition
Mice, Inbred C57BL
030104 developmental biology
Microscopy, Fluorescence
Cancer research
bacteria
lcsh:Q
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....0cdc9cdb869d905e8ac8c978bb51055b