Fig. 4

Associations of phosphoflow cytometry signaling with outcome in melanoma patients. In panels A and B, 14 melanoma patients were treated with high-dose IFN-α (HDI) and p-STAT1 signaling responsiveness to IFN-α was analyzed both prior to and after treatment. p-STAT1 induction at baseline and after 4 weeks of treatment was analyzed in total lymphocytes and CD8⁺ T cells from responding (R) and non-responding (NR) patients A. The relationship between IFN-α-induced p-STAT1 activation and clinical outcome was assessed by Kaplan–Meier analysis by generating a ratio (post/pre) of p-STAT1 fold induction in lymphocytes before and after treatment, and comparing patients above and below the median B. In a separate study, in panels C and D, melanoma patients were analyzed for p-STAT3 expression after surgical resection and adjuvant nivolumab. The geometric mean fluorescent intensity (gMFI) of p-STAT3 from baseline to week 13 in regulatory T cells (Tregs) and CD8⁺ T cells was compared between patients with no evidence of disease (NED) and relapse C. The correlation between overall survival and percent change in p-STAT3 at week 13 compared to baseline was assessed in Tregs, conventional T cells (Tcon), and CD8⁺ T cells D. Panels A and B are modified from Simons et al., J. Transl Med. 2011 [52]. Copyright© 2011, Simons et al., Licensee BioMed Central Ltd. Panels C and D are modified from Woods et al., Clin Cancer Res. 2018 [53]. Copyright© 2018, American Association for Cancer Research