Investigating Nano-Sized Tumor-Derived Extracellular Vesicles in Enhancing Anti-PD-1 Immunotherapy

Abstract

Anti-PD1 immune checkpoint blockade (ICB) has shown promising results for treating several aggressive cancers, enhancing patient survival rates. The variability in clinical response to anti-PD1 ICB is thought to be driven by patient-specific biology and heterogeneity within the tumor microenvironment. Tumor-derived extracellular vesicles (TDEVs), nano-sized particles released from tumor cells, can modulate the tumor microenvironment, leading to immunosuppression and tumor progression. Hence, TDEVs may contribute to the variability in treatment response and play a crucial role in the failure of anti-PD1 immunotherapy. In this study, we develop a systems biology approach to interrogate the role of TDEVs on the response dynamics for anti-PD1 blockade. Our results suggest that the detection and profiling of TDEVs can help screen patients for anti-PD-1 immunotherapy. Moreover, the results in this study suggest that TDEVs and IL-12 can potentially be liquid biopsy biomarkers to profile patient response to anti-PD1 ICB and tailor patient-specific treatment protocols.