Exosomal PD-L1 Derived From Osteosarcoma is Associated With Pulmonary Metastasis for Patients With Osteosarcoma

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background Recent studies indicated that exosomal programmed death-ligand 1 (PD-L1) derived from cancers could induce immunosuppression and tumor pathogenesis. However, it is unclear how the exosome influences the osteosarcoma (OS) progression and whether PD-L1 also exists in serum exosomes (Sr-exosomes) of patients with osteosarcoma. Methods We examined serum exosomes from 70 patients with osteosarcoma, 9 patients with benign tumors and 22 healthy donors. Osteosarcoma-derived exosomes and exosomal-PD-L1 were functionally evaluated using <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic> models. Results The characteristics of serum exosomes of OS patients and OS cell line exosomes were confirmed by several methods. Bioinformatic analysis demonstrated that Sr-exosomes isolated from OS patients may involve in the important process of immune function and cancer pathogenesis for OS patients. Meanwhile, exosomes derived from OS cell line and serum of OS patients could induce osteosarcoma migration and invision <jats:italic>in vitro</jats:italic>. Then, we confirmed PD-L1 existing in Sr-exosomes of patients with osteosarcoma and higher level of Sr-exosomal PD-L1 in OS patients compared to healthy donors and patients with benign tumor. Furthermore, exosomal-PD-L1 derived from osteosarcoma promoted the pulmonary metastasis, which was demonstrated in the osteosarcoma metastatic model. Conclusion We confirm that osteosarcoma releases the exosomes carrying PD-L1 on their surface and induces the pathogenesis of pulmonary metastasis for OS patients.</jats:p>