Le traitement combiné par radiation focale et anticorps anti--mCTLA-4 module les niveaux de phospho-stat3 du sous-ensemble myéloïde dans l'environnement tumoral 4T1 et entraîne l'inhibition de la croissance de la tumeur



David W Draper, Hillary Evens, Alden Wong, Scott Wise, and Maryland Rosenfeld Franklin




AACR Tumor Immunology and Immunotherapy

Introduction et contexte

  • Signaling through signal transducer and activator of transcription factor 3 (STAT3) in myeloid subsets triggers gene expression that has direct and indirect suppressive effects on several immune subsets.
  • Selective targeting of STAT3 in myeloid cells has become an attractive therapeutic approach as it can prevent adverse effects that may otherwise be triggered by broad inhibition of the pathway.
  • To facilitate development of drugs with selectivity for phospho-protein targets like STAT3, we have developed a phospho-flow panel that can measure phosphoprotein states in distinct myeloid subsets simultaneously.
  • The 4T1 syngeneic breast cancer model was used due to its high prevalence of granulocytic (G) MDSCs, as well as other immunosuppressive myeloid subsets.
  • Our results demonstrate that phospho-STAT3 (pSTAT3) levels were differentially regulated in MDSC and tumor-associated macrophage (TAM) subsets following in vivo treatment with focal radiation, anti-mCTLA-4, or the combination.