Tracking of Tumor-Derived Exosomal PD-L1 for Cancer Diagnosis and Surveilance of Immunotherapy Response by Dual-Aptamer-encoded Nanocatalyst Assembly.

e14528 Background: Immunohistochemistry is still the gold standard for identifying suitable populations for ICB therapy by staining PD-L1 in tumor tissue. However, IHC may be frustrated by intratumoral heterogeneity, subject to sampling error, and risk damaging tissue. Application of tumor-derived exosomal PD-L1 (Exo-PD-L1) for searching suitable populations for immunotherapy and monitoring immunotherapy response in breast cancer is often hindered by normal cells-derived Exo-PD-L1and the limitation of existed tools. Methods: We have developed a dual-target-specific aptamer recognition activated in situ hybridization chain reaction (HCR)-weaved nanocatalyst assembly (TRACE) on exosome for visualized tracking of Exo-PD-L1. Leveraging theexcellent selectivity of dual-aptamer recognition, high sensitivity of HCR-encoded nanocatalyst assembly, and high accessibility of color changes-based analysis. The clinical significance of tumor-derived Exo-PD-L1 were evaluated in a small cohort of clinical samples (4 healthy donors (HDs), 20 PD-L1-negative (PD-L1-N) breast cancer patients, and 10 PD-L1-positive (PD-L1-P) breast cancer patients) by using this TRACE system. All serum is collected and CT is scanned at approximately every 2 cycles. Results: The TRACE system can accurately distinguish PD-L1-positive breast cancer patients from healthy donors and PD-L1-negative patients by selectively and sensitively detecting tumor-derived Exo-PD-L1, with the most appropriate cutoff value of 0.6168 and 0.3603, respectively. The receiver operating characteristic (ROC) curve demonstrates the excellent accuracy (AUC: 1) of this TRACE system due to the high sensitivity and specificity. Moreover, the TRACE system provide a quantified and visualized tool for dynamically revealing immunotherapy response based on the levels of tumor-derived Exo-PD-L1, including stable, progressive, and partial response. Conclusions: The TRACE system may have a great potential for supplementing the existing standards and assisting to screen appropriate patients for ICB therapy and explore situable patients from different therapeutic regimenin-depth. As a companion diagnostics tool, the TRACE system may also rise great hope for improving the management of dosage, therapeutic regimen, and efficacy evaluation by providing timely feedback of immunotherapy response.