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Peer-reviewedCC BYThe Journal of Liquid Biopsy

Clinical utility of circulating tumor cell PD-L1 expression for predicting immunotherapeutic response and prognosis in esophageal cancer

  • Jing Li1
  • Yueze Li1
  • Lin Chen2
  • Zhonglin Yang2
  • Yue Lu2
  • Dongjiang Tang3
  • Yanru Qin4
4 affiliations
  1. 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, longhu zhonghuan road, No.1, Zhengzhou, Henan, 450000, P. R. China
  2. 2Zhuhai Sanmed Biotech Ltd., 266 Tongchang Road, Zhuhai, Guangdong, 519060, P. R. China
  3. 3Zhuhai Sanmed Biotech Ltd., 266 Tongchang Road, Zhuhai, Guangdong, 519060, P. R. China; Corresponding author.
  4. 4Department of Oncology, The First Affiliated Hospital of Zhengzhou University, longhu zhonghuan road, No.1, Zhengzhou, Henan, 450000, P. R. China; Corresponding author.
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Abstract

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in esophageal cancer, yet reliable biomarkers remain lacking. Tissue PD-L1 testing is limited by intratumoral heterogeneity and invasiveness, whereas circulating tumor cells (CTCs) offer a non-invasive alternative. This study evaluated CTC PD-L1 expression as a predictive and prognostic biomarker in patients with advanced esophageal cancer receiving chemo-immunotherapy. Methods: A total of 93 patients with stage III–IV esophageal cancer were enrolled. The primary biomarker analysis was restricted to 59 patients who received chemo-immunotherapy, while 34 patients treated with chemotherapy alone were analyzed separately. Baseline CTCs were isolated and PD-L1 expression assessed, alongside tissue PD-L1 (tPD-L1) by immunohistochemistry. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated using ROC curves and univariate and multivariable Cox regression. Results: CTC positivity correlated significantly with advanced stage, metastasis ( p = 0.0411), and larger tumor size ( p = 0.0454). In the chemo-immunotherapy cohort, CTC PD-L1 positivity was associated with a higher ORR (75.0% vs. 29.6%, p < 0.001) and showed moderate predictive ability (AUC = 0.7049, p = 0.0037). CTC PD-L1 positivity was significantly associated with OS (HR = 0.254, p = 0.002), but not significantly with PFS in univariate analysis (HR = 0.546, p = 0.042; Kaplan–Meier p = 0.061). Conversely, tPD-L1 status was not significantly associated with PFS or OS (both p > 0.05). In multivariable analysis adjusting for age, sex, histological subtype, stage, metastasis, and treatment modality, CTC PD-L1 remained an independent prognostic factor for PFS (HR = 0.488, p = 0.039) and OS (HR = 0.244, p = 0.002). Conclusions: Baseline CTC PD-L1 expression was associated with favorable response and OS in patients receiving chemo-immunotherapy, and may complement tissue testing. These exploratory findings require prospective validation in larger cohorts before clinical use.

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Cite

BibTeXRIS
BibTeX
@article{li2026clinical,
  title = {{Clinical utility of circulating tumor cell PD-L1 expression for predicting immunotherapeutic response and prognosis in esophageal cancer}},
  author = {Jing Li and Yueze Li and Lin Chen and Zhonglin Yang and Yue Lu and Dongjiang Tang and Yanru Qin},
  journal = {The Journal of Liquid Biopsy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jlb.2026.100681},
  url = {https://doi.org/10.1016/j.jlb.2026.100681},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Clinical utility of circulating tumor cell PD-L1 expression for predicting immunotherapeutic response and prognosis in esophageal cancer
AU  - Jing Li
AU  - Yueze Li
AU  - Lin Chen
AU  - Zhonglin Yang
AU  - Yue Lu
AU  - Dongjiang Tang
AU  - Yanru Qin
PY  - 2026
DA  - 2026/10/21
JO  - The Journal of Liquid Biopsy
DO  - 10.1016/j.jlb.2026.100681
UR  - https://doi.org/10.1016/j.jlb.2026.100681
AB  - Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in esophageal cancer, yet reliable biomarkers remain lacking. Tissue PD-L1 testing is limited by intratumoral heterogeneity and invasiveness, whereas circulating tumor cells (CTCs) offer a non-invasive alternative. This study evaluated CTC PD-L1 expression as a predictive and prognostic biomarker in patients with advanced esophageal cancer receiving chemo-immunotherapy. Methods: A total of 93 patients with stage III–IV esophageal cancer were enrolled. The primary biomarker analysis was restricted to 59 patients who received chemo-immunotherapy, while 34 patients treated with chemotherapy alone were analyzed separately. Baseline CTCs were isolated and PD-L1 expression assessed, alongside tissue PD-L1 (tPD-L1) by immunohistochemistry. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated using ROC curves and univariate and multivariable Cox regression. Results: CTC positivity correlated significantly with advanced stage, metastasis ( p = 0.0411), and larger tumor size ( p = 0.0454). In the chemo-immunotherapy cohort, CTC PD-L1 positivity was associated with a higher ORR (75.0% vs. 29.6%, p < 0.001) and showed moderate predictive ability (AUC = 0.7049, p = 0.0037). CTC PD-L1 positivity was significantly associated with OS (HR = 0.254, p = 0.002), but not significantly with PFS in univariate analysis (HR = 0.546, p = 0.042; Kaplan–Meier p = 0.061). Conversely, tPD-L1 status was not significantly associated with PFS or OS (both p > 0.05). In multivariable analysis adjusting for age, sex, histological subtype, stage, metastasis, and treatment modality, CTC PD-L1 remained an independent prognostic factor for PFS (HR = 0.488, p = 0.039) and OS (HR = 0.244, p = 0.002). Conclusions: Baseline CTC PD-L1 expression was associated with favorable response and OS in patients receiving chemo-immunotherapy, and may complement tissue testing. These exploratory findings require prospective validation in larger cohorts before clinical use.
SN  - 2950-1954
ER  -