The Use of TF-Ag-α to Selectively Capture Tumor-Derived Extracellular Vesicles and Enhance the Predictive Performance of Extracellular Vesicle PD-L1 for Response to Immune Checkpoint Inhibitors
4 affiliations
- 1Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, New York.
- 2Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
- 3Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
- 4For-Robin, Inc., Buffalo, New York.
Abstract
Only a subset of patients with non–small cell lung cancer (NSCLC) benefits from immune checkpoint inhibitors (ICIs). Tissue PD-L1 has limited accuracy in predicting ICI response and requires invasive biopsies, highlighting the urgent need for reliable, minimally invasive biomarkers. Extracellular vesicle (EV) PD-L1 is a promising liquid biopsy marker, but its predictive performance is confounded by PD-L1 derived from nontumor cells. We developed a tumor-specific EV-based assay to predict ICI response. Tumor-derived EVs (TEX) were selectively captured using the tumor-specific Thomsen–Friedenreich glycoantigen α (TF-Ag-α), and PD-L1 levels in TEX expressing TF-Ag-α (i.e., TEXTF-Ag-α PD-L1) were measured in sera from 91 patients with NSCLC receiving anti–PD-1 therapy (40 responders and 51 nonresponders). Predictive performance was evaluated at pretreatment baseline, at the end of the first treatment cycle, and via fold changes (FC). At pretreatment baseline, TEXTF-Ag-α PD-L1 showed moderate predictive ability [area under the curve (AUC): 0.76; sensitivity: 0.97; specificity: 0.56]. By the end of the first treatment cycle, responders exhibited a ∼4.18-fold increase in TEXTF-Ag-α PD-L1 expression, whereas nonresponders showed an approximate 20% decrease. Dynamic FCs after the first treatment cycle substantially improved predictive performance, achieving an AUC of 0.93, sensitivity of 0.95, and specificity of 0.80 for distinguishing responders from nonresponders, outperforming both total EV PD-L1 and tissue PD-L1. These results demonstrated that selective TEX capture using TF-Ag-α significantly enhanced the predictive value of EV PD-L1. Dynamic changes in TEXTF-Ag-α PD-L1 provided a highly accurate, minimally invasive biomarker for early assessment of anti–PD-1 response, supporting tumor-specific EV-based liquid biopsy for precision immunotherapy.
Significance:: Reliable biomarkers for predicting ICI response remain lacking. We developed a tumor-specific liquid biopsy assay that selectively captures TEX via TF-Ag-α, enabling accurate PD-L1 measurement. By reducing interference from nontumor EVs, the assay achieved 93% predictive accuracy, outperforming tissue PD-L1 and supporting precision immunotherapy.
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BibTeX
@article{hsu2026tfagα,
title = {{The Use of TF-Ag-α to Selectively Capture Tumor-Derived Extracellular Vesicles and Enhance the Predictive Performance of Extracellular Vesicle PD-L1 for Response to Immune Checkpoint Inhibitors}},
author = {Chang-Chieh Hsu and Man Qi and Fumito Ito and Grace K. Dy and Kate Rittenhouse-Olson and Yun Wu},
journal = {Cancer Research Communications},
year = {2026},
month = nov,
doi = {10.1158/2767-9764.crc-26-0214},
url = {https://doi.org/10.1158/2767-9764.crc-26-0214},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Use of TF-Ag-α to Selectively Capture Tumor-Derived Extracellular Vesicles and Enhance the Predictive Performance of Extracellular Vesicle PD-L1 for Response to Immune Checkpoint Inhibitors
AU - Chang-Chieh Hsu
AU - Man Qi
AU - Fumito Ito
AU - Grace K. Dy
AU - Kate Rittenhouse-Olson
AU - Yun Wu
PY - 2026
DA - 2026/11/02
JO - Cancer Research Communications
DO - 10.1158/2767-9764.crc-26-0214
UR - https://doi.org/10.1158/2767-9764.crc-26-0214
AB - Only a subset of patients with non–small cell lung cancer (NSCLC) benefits from immune checkpoint inhibitors (ICIs). Tissue PD-L1 has limited accuracy in predicting ICI response and requires invasive biopsies, highlighting the urgent need for reliable, minimally invasive biomarkers. Extracellular vesicle (EV) PD-L1 is a promising liquid biopsy marker, but its predictive performance is confounded by PD-L1 derived from nontumor cells. We developed a tumor-specific EV-based assay to predict ICI response. Tumor-derived EVs (TEX) were selectively captured using the tumor-specific Thomsen–Friedenreich glycoantigen α (TF-Ag-α), and PD-L1 levels in TEX expressing TF-Ag-α (i.e., TEXTF-Ag-α PD-L1) were measured in sera from 91 patients with NSCLC receiving anti–PD-1 therapy (40 responders and 51 nonresponders). Predictive performance was evaluated at pretreatment baseline, at the end of the first treatment cycle, and via fold changes (FC). At pretreatment baseline, TEXTF-Ag-α PD-L1 showed moderate predictive ability [area under the curve (AUC): 0.76; sensitivity: 0.97; specificity: 0.56]. By the end of the first treatment cycle, responders exhibited a ∼4.18-fold increase in TEXTF-Ag-α PD-L1 expression, whereas nonresponders showed an approximate 20% decrease. Dynamic FCs after the first treatment cycle substantially improved predictive performance, achieving an AUC of 0.93, sensitivity of 0.95, and specificity of 0.80 for distinguishing responders from nonresponders, outperforming both total EV PD-L1 and tissue PD-L1. These results demonstrated that selective TEX capture using TF-Ag-α significantly enhanced the predictive value of EV PD-L1. Dynamic changes in TEXTF-Ag-α PD-L1 provided a highly accurate, minimally invasive biomarker for early assessment of anti–PD-1 response, supporting tumor-specific EV-based liquid biopsy for precision immunotherapy. Significance:: Reliable biomarkers for predicting ICI response remain lacking. We developed a tumor-specific liquid biopsy assay that selectively captures TEX via TF-Ag-α, enabling accurate PD-L1 measurement. By reducing interference from nontumor EVs, the assay achieved 93% predictive accuracy, outperforming tissue PD-L1 and supporting precision immunotherapy.
SN - 2767-9764
ER -