Targeting phosphatidylserine synergizes with immune checkpoint blockade by inducing de novo tumor specific immunity

Background Extensive studies have demonstrated that the inside-out membrane phospholipid phosphatidylserine (PS) actively drives global immunosuppression in the tumor microenvironment and is a major contributor to tumor resistance to immune checkpoint blockade. We have shown that PS targeting antibodies can re-program the tumor microenvironment from immunosuppressive to immune potentiating by reducing the number of myeloid-derived suppressor cells (MDSCs), repolarizing tumor associated macrophages from M2 to M1 and by promoting the maturation of dendritic cells. We have found that PS targeting antibodies synergize with and significantly enhance the therapeutic efficacy of immune checkpoint blockade in multiple tumor models. In the present study, we examined the effect of combination of a PS targeting antibody and anti-PD-1 or anti-CTLA-4 on tumor-specific CD8 T cell immunity.