Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer

Figure 5

Immunomodulatory effect of paclitaxel. Paclitaxel, a toll-like receptor 4 (TLR4) ligand binds to TLR4 receptor and triggers TLR4 signaling via MyD88 dependent and independent pathway. Paclitaxel then promotes anticancer immune response directly by stimulating macrophages to kill cancer cells or indirectly by secretion of proinflammatory cytokines which upregulates activation of DCs, NK and tumour specific CTL. Paclitaxel promotes effective CTL response by upregulation of mannose-6-phosphate which facilitate permeability to granzyme B and cytokine patterns of T helper type 1. Paclitaxel modulates MDSC and ablates Tregs. Memory T cells (CD4+CD45RO+ and CD8+CD45RO+) increased significantly while regulatory T cells (Tregs) decreased around 2 weeks, creating an opportunity window for dose-dense therapy and immunomodulatory agents to achieve clinical benefit. Dose-dense and low dose paclitaxel also blocks new vessel formation by downregulating VEGF-receptor 2, reduces resistance by alternative mechanism of action.