Cancer cells exploit the PD-1 pathway to create an immunosuppressive environment. There is often an increase in the production of inhibitory pathways and suppression of stimulatory pathways, allowing cancer cells to dampen down the immune response at inappropriate times to create an immunosuppressive environment in which they are able to thrive. Cancer cells drive high expression levels of PD-L1 on their surface, allowing activation of the inhibitory PD-1 receptor on any T cells that infiltrate the tumor microenvironment, effectively switching those cells off.5,8,22 Indeed, upregulation of PD-L1 expression levels has been demonstrated in many different cancer types (eg, melanoma [40%-100%], NSCLC [35%-95%], and multiple myeloma [93%]), and high levels of PD-L1 expression have been linked to poor clinical outcomes.7,25-28 Furthermore, tumor-infiltrating T cells have been shown to express significantly higher levels of PD-1 than T cells that infiltrate normal tissue. It is thought that the tumor microenvironment may secrete pro-inflammatory cytokines, including interferon-gamma (IFNg) to upregulate the expression of PD-1 on tumor-infiltrating T cells to ensure that they can respond to the high levels of PD-L1 expressed on the tumor. -
The Role of Anti-PD-L1 Immunotherapy in Cancer (2014)
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