Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy

Abstract

The abscopal effect of radiation therapy (RT) is clinically significant but occurs rarely. Although anti-programmed cell death protein 1 antibody (anti-PD1) is likely to enhance the abscopal effect in patients receiving RT, the incidence rate remains less than 30%. One major limitation is the paucity of CD8⁺ T cells within non-irradiated tumors. Here, cisplatin (CDDP) loaded poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) are confirmed to increase CD8⁺ T cells within non-irradiated tumors and boost the abscopal effect of RT plus anti-PD1, and more strongly than CDDP. Compared to RT and RT + CDDP, RT + CDDP-NPs induced greater immunogenic cell death (ICD) with enhanced proportion of Calreticulin⁺ Lewis lung cancer (LLC) cells (16.47%, 20.53% and 27.03%), along with which more CD8⁺ T cells were infiltrated into CDDP-NP treated irradiated tumors in the unilateral LLC tumor model. In the bilateral LLC tumor model, RT + CDDP-NPs significantly induced more chemokine (C–X–C motif) ligand 10 (CXCL10) secretion (36.3, 44.19 and 56.37 pg mL⁻¹), which corresponded to greater CD8⁺ T cell infiltration in the non-irradiated tumors (0.19%, 0.20% and 0.72%). Finally, compared to RT + anti-PD1 and RT + anti-PD1 + CDDP, RT + anti-PD1 + CDDP-NPs significantly inhibited the growth of non-irradiated tumors more forcefully, as indicated by the respective tumor volumes of 1141, 1146 and 585 mm³. This is the first study to show that CDDP-NPs can amplify RT-induced immune activation and break through the efficiency limitation of the RT plus anti-PD1 induced abscopal effect.