Cart before the horse...checkpoint inhibitors
Cold tumors do not express PD-L1....why would they? PD-L1 is expressed as a result of IFN-gamma in the tumor environment. IFN-gamma is produced by mature primed CD8+T cells. Mature primed CD8+Tís have to be primed with cancer specific antigens by APCís first. APCís must first recognize cancer specific antigens before they can cross present them to CD8+Tís with the help of CD4+Tís. Ergo the tumor must be at least luke warm or at best hot for PD-L1 to be expressed before checkpoint inhibitors are effective. Cart before the horse. The tumor must first have the cancer specific antigens recognized before checkpoint inhibitors are functional.
In the rare cases it works on a ďcold tumorĒ...the tumor was not cold...but smoldering.