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CD27 expression on Treg cells limits immune responses against tumors
- Source :
- Journal of molecular medicine (Berlin, Germany). 100(3)
- Publication Year :
- 2021
-
Abstract
- Abstract Regulatory T cells (Tregs) suppress immune responses and thus contribute to immune homeostasis. On the downside, Tregs also limit immune responses against tumors promoting the progression of cancer. Among the many mechanisms implied in Treg-mediated suppression, the inhibition of dendritic cells (DCs) has been shown to be central in peripheral tolerance induction as well as in cancers. We have shown previously that the maintenance of peripheral T cell tolerance critically depends on cognate interactions between Tregs and DCs and that the CTL priming by unsuppressed steady state DCs is mediated via CD70. Here, we have investigated whether the CD70/CD27 axis is also involved in Treg-mediated suppression of anti-tumor immunity. Using a mixed bone marrow chimeric mouse model in which we can deplete regulatory T cells in a temporally controlled fashion, we show that Treg-expressed CD27 prevents the breakdown of peripheral tolerance and limits anti-tumor immunity. Furthermore, ablation of Treg expressed CD27 acts synergistically with PD-1 checkpoint inhibition to improve CTL mediated immunity against a solid tumor. Our data thus identify Treg-expressed CD27 as a potential target in cancer immunotherapy. Key messages Treg expressed CD27 maintains steady state DC tolerogenic Treg expressed CD27 limits anti-tumor immunity Ablation of Treg expressed CD27 synergizes with PD-1 blockade to improve CTL mediated tumor control
- Subjects :
- T cell
medicine.medical_treatment
610 Medizin
chemical and pharmacologic phenomena
Biology
T-Lymphocytes, Regulatory
Mice
Immune system
Cancer immunotherapy
Immunity
610 Medical sciences
Neoplasms
Drug Discovery
medicine
Animals
Genetics (clinical)
Peripheral tolerance induction
Peripheral tolerance
hemic and immune systems
Immunotherapy
Dendritic Cells
CTL
medicine.anatomical_structure
Cancer research
Molecular Medicine
Subjects
Details
- ISSN :
- 14321440
- Volume :
- 100
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of molecular medicine (Berlin, Germany)
- Accession number :
- edsair.doi.dedup.....5f81d85f4a2bc9cb99a27de49b81a208