Photodynamic And Autophagy Inhibition Therapy Induces Inflammation Pathway And Nhance The Immunotherapy Of Osteosarcoma By PD-L1 Regulation

As one of the most common primary malignant tumors in childhood,osteosarcoma is an important factor that threatens the health of children and adolescents.Although the overall survival rate has been improved with the advances in the combined treatment of osteosarcoma with neoadjuvant chemotherapy and surgery,patients are still facing a series of problems such as tumor drug resistance,distance metastasis or in situ recurrence.As a new tumor treatment method,photodynamic therapy(PDT)has showed therapeutic potential in the treatment of osteosarcoma.In this study,zinc phthalocyanine(Zn Pc)was used as the core of photosensitizer,and a novel photosensitizer particle BSA-Zn Pc(BZ)was synthesized by encapsulating bovine serum albumin(BSA)in osteosarcoma PDT.We confirmed the cytotoxicity effect of BZ-induced PDT in the osteosarcoma treatment in vitro and the combined therapeutic effect togather with surgery in vivo.Further,we investigated BZ nanoparticle mediated autophagy in osteosarcoma cells and investigated the mechanism of the PD-L1 regulation and the enhancement in PDT-induced immunotherapy induced by autophagy inhibitor,3-Methyladenine.Finally,as the important role of the inflammatory pathway found in the PD-L1 regulation on the PDT-induced osteosarcoma treatment,we further studied the regulation mechanism of key inflammatory factor,PTGS2-mediated PD-L1 expression in osteosarcoma cells.At the same time,the important role of STAT6 in this process is illustrated in detail.In general,this study found the combination between the anti-tumor materials and tumor immunotherapy on the osteosarcoma treatment and then elucidates the PD-L1-induced immune regulation mechanism in this process.These results provide the theoretical and research basis for the new treatment of osteosarcoma patients in the future.