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July 30, 2026The Journal of Immunology

A Glucocorticoid-Fas axis controls immune evasion from pan-cytotoxic lymphocytes during metastatic seeding 2334193

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Authors

JAJudith AgudoMCMonica Cassandras

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Overview

Randomized trial reveals the glucocorticoid-fas pathway's role in immune evasion in metastatic tumor cells, suggesting new treatment strategies.

Key Points

  • This research aims to understand how disseminated tumor cells evade immune detection during early metastatic seeding.
  • Utilized a visible antigen in a TNBC model with CD8+ T cells.
  • Implemented glucocorticoid receptor knockdown in tumor cells.
  • Conducted single cell analysis of disseminated tumor cells in the lung.
  • DTCs showing GR activation were resistant to CD8+ T and NK cell killing, with pharmacologic GR inhibition leading to reduced metastatic burden (p<0.05).
  • Fas-FasL pathway identified as a crucial mediator of T cell cytotoxicity against DTCs, with GR blocking Fas receptor expression.
  • Inhibition of GR combined with immune checkpoint blockade significantly extended lifespan in treated mice.

Cite This Study

Agudo et al. (2026) studied this question.

synapsesocial.com/papers/6a6af52c60e2b924d3ea0eefhttps://doi.org/10.1093/jimmun/vkag141.1847
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract B016: Pharmacologic inhibition of the Glucocorticoid Receptor synergizes with immunotherapy to prevent metastatic recurrence in pre-clinical models2026
  2. 2Targeting glucocorticoid receptor to enhance immunotherapy response in triple negative breast cancer2026 · 2 citations
  3. 3Single-Cell Profiling Reveals a Treg-Rich, NK Cell-Depleted Immune Microenvironment in Triple-Negative Breast Cancer with High-Glucocorticoid Receptor Expression2026
  4. 4Immunotherapy Resistant Triple Negative Breast Cancer Utilizes Interferon Gamma Signaling to Evade NK Responses during Metastasis 23350472026
  5. 5PHGDH-High Dormant Tumor Cells Evade Immunity and Drive Metastasis2026