Fig. 3: Soluble mediators of immunosuppression are elevated in patients with ICI-refractory melanoma, are reduced by TPE, and reaccumulate.

A Soluble factors at baseline in patients with ICI-refractory melanoma and matched healthy controls were measured by O-link multiplex assay. The log difference in mean level (x axis) and two-sided p value of the difference by Student’s t test (y axis) is shown for each soluble factor. B Post-TPE levels of sPD-L1 predicted OS (log rank p = 0.007). C–E sPD-L2 was significantly reduced (Wilcoxon p = 0.0006) by TPE and recovered (p = 0.0004) before the second cycle of re-challenge ICI. Post-TPE levels of sPD-L1 predicted OS (log rank p = 0.002) while pre-cycle 2 sPD-L2 did not (p = 0.1). F–H Soluble TIM3 was significantly reduced by TPE (Wilcoxon p = 0.0002) and recovered (p = 0.0004) before the second cycle of re-challenge ICI. Post-TPE levels of TIM3 predicted OS (log rank p = 0.008) while pre-cycle 2 TIM3 did not (p = 0.07). All statistical tests were two-sided, no adjustments were made for multiple comparisons. See Supplementary Fig. 8, Supplementary Data 1. C2 cycle 2, OS overall survival, TPE therapeutic plasma exchange.