Figure 6.

Schematic diagram: Suggested model of how C24D reverses tumor-induced immune suppression through the CD45 signaling pathway. a. In PBMCs from healthy donors exposed to TNBC tumors, phosphorylation of the inhibitory tyrosine (y) 505 in Lck (a member of the Src tyrosine kinases) increased, phosphorylation of the tyrosine 394 in Lck decreased, de-activating the Lck protein in the peripheral blood leukocytes. In consequence, tyrosine 493 in ZAP70, and VAV-1 were de-phosphorylated, de-activating ZAP70 and VAV-1. As a result, TCR activity decreased, dampening immune response. b. Binding of the C24D peptide to the CD45 receptor on leukocytes which were previously exposed to TNBC cells, reverses the suppression by de-phosphorylation of the tyrosine 505 and phosphorylation of the tyrosine 394 in Lck. Consequently, the tyrosine 493 in ZAP70 and VAV-1 are phosphorylated, resulting in TCR activation, tumor cell killing and secretion of IFN-γ, IL-2 and TNF-α