Combining High-Z Sensitized Radiotherapy with CD73 Blockade to Boost Tumor Immunotherapy

Radiationtherapy (RT) has the capacity to induce immunogenic deathin tumor cells, thereby potentially inducing in situ vaccination (ISV) to prime systemic antitumor immune responses.However, RT alone is often faced with various limitations during ISVinduction, such as insufficient X-ray deposition and an immunosuppressivemicroenvironment. To overcome these limitations, we constructed nanoscalecoordination particles AmGd-NPs by self-assembling high-Z metal gadolinium(Gd) and small molecular CD73 inhibitor AmPCP. Then, AmGd-NPs couldsynergize with RT to enhance immunogenic cell death, improve phagocytosis,and promote antigen presentation. Additionally, AmGd-NPs could alsogradually release AmPCP to inhibit CD73's enzymatic activityand prevent the conversion of extracellular ATP to adenosine (Ado),thereby driving a proinflammatory tumor microenvironment that promotesDC maturation. As a result, AmGd-NPs sensitized RT induced potent in situ vaccination and boosted CD8(+) T cell-dependentantitumor immune responses against both primary and metastatic tumors,which could also be potentiated by immune checkpoint inhibitory therapy.

Automated summary

Radiation therapy has the potential to induce immunogenic cell death in tumor cells, leading to in situ vaccination and systemic antitumor immune responses. However, there are limitations to using radiation therapy alone, such as insufficient X-ray deposition and an immunosuppressive microenvironment. To overcome these limitations, researchers developed AmGd-NPs, nanoscale coordination particles that could enhance immunogenic cell death, improve phagocytosis, and promote antigen presentation when combined with radiation therapy. AmGd-NPs also inhibited CD73 activity and promoted a proinflammatory tumor microenvironment, leading to potent in situ vaccination and boosted antitumor immune responses.