Enhanced Immunogenic Cell Death by Apoptosis/Ferroptosis Hybrid Pathway Potentiates PD-L1 Blockade Cancer Immunotherapy

This is the authors' abstract. We don't add key points for this paper.

Even though chemotherapy regimens for treating cancer by inducing apoptosis are extensively utilized, their therapeutic effect is hindered by multiple limitations. Thus, a combination of other types of anticancer modalities is urgently needed. Herein, a tannic acid (TA)-Fe 3+ -coated doxorubicin (DOX)-encapsulated 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(poly(ethylene glycol))-2000] (ammonium salt) (DSPE-PEG) micelle (TFDD) for apoptosis/ferroptosis-mediated immunogenic cell death (ICD) is reported. By coating TA-Fe 3+ on the surface of DOX-loaded micelles, an apoptotic agent and a ferroptotic agent are simultaneously delivered into the cancer cells and induce cell death. Furthermore, the intracellular oxidative environment generated by the apoptosis/ferroptosis hybrid pathway stimulates the endoplasmic reticulum (ER) and leads to ICD induction. The in vivo results show that the combination treatment of TFDD and anti-programmed death-ligand 1 antibodies (anti-PD-L1) considerably inhibits tumor growth and improves antitumor immunity by activating CD4 + and CD8 + T cells and decreasing the ratio of regulatory T cells (Treg) to CD4 + T cells. This study suggests that the apoptosis/ferroptosis-mediated ICD inducer may offer a potent strategy for enhanced cancer immunotherapy.