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Dexamethasone premedication suppresses vaccine-induced immune responses against cancer.
- Source :
- OncoImmunology; 2020, Vol. 9 Issue 1, p1-11, 11p
- Publication Year :
- 2020
-
Abstract
- Glucocorticosteroids (GCS) have an established role in oncology and are administered to cancer patients in routine clinical care and in drug development trials as co-medication. Given their strong immune-suppressive activity, GCS may interfere with immune-oncology drugs. We are developing a therapeutic cancer vaccine, which is based on a liposomal formulation of tumor-antigen encoding RNA (RNA-LPX) and induces a strong T-cell response both in mice as well as in humans. In this study, we investigated in vivo in mice and in human PBMCs the effect of the commonly used long-acting GCS Dexamethasone (Dexa) on the efficacy of this vaccine format, with a particular focus on antigen-specific T-cell immune responses. We show that Dexa, when used as premedication, substantially blunts RNA-LPX vaccine-mediated immune effects. Premedication with Dexa inhibits vaccine-dependent induction of serum cytokines and chemokines and reduces both the number and activation of splenic conventional dendritic cells (cDC) expressing vaccine-encoded antigens. Consequently, priming of functional effector T cells and therapeutic activity is significantly impaired. Interestingly, responses are less impacted when Dexa is administered post-vaccination. Consistent with this observation, although many inflammatory cytokines are reduced, IFNα, a key cytokine in T-cell priming, is less impacted and antigen expression by cDCs is intact. These findings warrant special caution when combining GCS with immune therapies relying on priming and activation of antigen-specific T cells and suggest that careful sequencing of these treatments may preserve T-cell induction. [ABSTRACT FROM AUTHOR]
- Subjects :
- IMMUNE response
PREMEDICATION
VACCINE effectiveness
DEXAMETHASONE
CANCER vaccines
Subjects
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 9
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 147926179
- Full Text :
- https://doi.org/10.1080/2162402X.2020.1758004