Combined Focal Radiation and Anti-mCTLA-4 Antibody Therapy Modulates Myeloid Subset Phospho-STAT3 Levels in the 4T1 Tumor Microenvironment, and Results in Tumor Growth Inhibition

AACR 2018 -- 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.

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In Vivo
Preclinical & Nonclinical