Modulation of IL-6/STAT3 signaling axis in CD4+FOXP3- T cells represents a potential antitumor mechanism of azacitidine.

CD4+ T cells orchestrate immune responses and are actively engaged in shaping tumor immunity. Signal transducer and activator of transcription (STAT) signaling controls the epigenetic tuning of CD4+ T-cell differentiation and polarization, and perturbed STAT signaling networks in CD4+ T cells subvert antitumor immunity in malignancies. Azacitidine (AZA), the mainstay therapy for high-risk myelodysplastic syndromes (HR-MDS), affects CD4+ T-cell polarization and function, but whether this contributes to AZA efficacy is currently unknown.

The STAT signaling profile at the single cell level reveals novel insights in the association of FOXP3+ T regulatory cells with recurrent spontaneous abortions before and after lymphocyte immunotherapy.

Foxp3+ T regulatory cell (Tregs) are central in the pathobiology of recurrent spontaneous abortions (RSA). Signal transducer and activator of transcription (STAT) proteins instruct Treg differentiation and polarization, but the STAT signaling architecture of Tregs in RSA and its modifications by lymphocyte immunotherapy (LIT) are yet unknown. By using single-cell phospho-specific flow cytometry we show that the STAT signaling biosignature of Tregs in women with RSA was characterized by marked downregulation of the IFNα/pSTAT1&5, IL-6/pSTAT1&3 and IL-2/pSTAT5 signaling nodes compared to age-matched fertile females.