Cellular messengers improve cancer therapy
Extracellular vesicles are important mediators of intercellular communication and are potential candidates for cancer immunotherapy. Immune checkpoint blockade, specifically of the PD-1/PD-L1 axis, mitigates T cell exhaustion, but is only effective in a subset of cancer patients. Reasons for therapy resistance include low primary T-cell activation to cancer antigens, poor antigen presentation, and reduced T-cell infiltration into the tumor.
Here, we investigated whether EV therapy could induce susceptibility to anti-PD-1 or –PD-L1 therapy in a checkpoint-refractory B16 melanoma model. Injection of dendritic cell -derived EVs, but not checkpoint blockade induced a potent antigen-specific T cell response and reduced tumor growth in tumor-bearing mice. Combination therapy of EVs and anti-PD-1 or –PD-L1 potentiated immune responses to OVA- and α-galactosylceramide-loaded EVs in the therapeutic model.
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