ArticleJournal for immunotherapy of cancer2025
Corticosteroid premedication on anti-tumor effect of immune checkpoint blockade in murine hepatocellular carcinoma models.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Antiemesis Corticosteroids Potentiate Checkpoint Blockade Efficacy by Normalizing the Immune Microenvironment in Metastatic Murine Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Application of Immune Checkpoint Inhibitors in Cancer.MedComm · 2025Review
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8 authors.
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Abstract
BACKGROUND AND
aimsCorticosteroid is effective in alleviating immune-related adverse events (irAEs) of immune checkpoint blockade (ICB). However, prophylactic use of corticosteroid to prevent irAEs is not recommended due to a looming concern that it may attenuate anti-tumor effect of ICB. This study aims to investigate whether corticosteroid premedication may compromise anti-tumor efficacy of dual ICB, a regimen that may cause significant irAEs.
methodsOrthotopic BNL 1MEA.7R.1 and subcutaneous Hepa1-6 syngeneic hepatocellular carcinoma (HCC) models were used. Low-dose (LD; 10 µg) or high-dose (HD; 200 µg) dexamethasone (Dexa) was intraperitoneally administered before each dose of anti-CTLA-4 and anti-PD-1. Tumor shrinkage, T cell priming, cytokine quantitation, as well as cytotoxicity and single-cell RNA-sequencing (scRNA-seq) of tumor-infiltrating T cells were assessed.
resultsIn the orthotopic model, dual immune checkpoint blockade (dICB) plus phosphate buffered saline (PBS) significantly reduced the mean tumor weight (adjusted for SE) (0.73±0.18 g vs 2.45±0.54 g; p=0.03), while neither LD nor HD Dexa premedication affected dICB-induced tumor shrinkage. In the subcutaneous model, dICB plus PBS or LD Dexa yielded a complete tumor response (CR) rate of 100%, while dICB plus HD Dexa yielded a CR rate of 85.7% (p>0.05, comparing to dICB plus PBS). ScRNA-seq analysis demonstrates that Dexa did not affect dICB-induced reduction of major clusters of exhausted CD4+ and CD8+ T cells but halved dICB-induced expansion of effector memory CD8+ T cells. Nevertheless, Dexa premedication, regardless of dosage, did not diminish dICB-induced T cell priming, cytokine production, or cytotoxicity of tumor-infiltrating CD8+ T cells.
conclusionCorticosteroid premedication does not significantly compromise anti-tumor efficacy of dICB treatment in murine HCC models. These results suggest that clinical investigations of prophylactic corticosteroids to alleviate severe irAEs may be feasible.
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