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Peer-reviewedCC BY 4.0Frontiers in Oncology

Pretransplant plasma soluble PD-1 and recurrence after liver transplantation in ICI-treated hepatocellular carcinoma: an exploratory biomarker study

  • Lizhen Zhu1,2,3,4,5
  • Ruolin Wang2,3,4,6
  • Wenzhi Shu2,3,4,6
  • Yi Gao7
  • Geng Zhang2,3,4,6
  • Wenlong Zhao2,3,4,6
  • Yucheng Hou2,3,4,6
  • Qian Lu2,3,4,6
7 affiliations
  1. 1Qinghai University Affiliated Hospital (Clinical Medical College)
  2. 2Hepatopancreatobiliary Center, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine,Tsinghua University
  3. 3Beijing Key Laboratory of Liver Transplantation and Bionic Manufacturing
  4. 4Institute for Organ Transplant and Bionic Medicine, Tsinghua University
  5. 5Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qinghai University
  6. 6School of Clinical Medicine, Tsinghua University
  7. 7Department of Orthopedics, Yingde People’s Hospital
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Abstract

Background: Immune checkpoint inhibitors (ICIs) are increasingly used as bridging or downstaging therapy before liver transplantation (LT) for hepatocellular carcinoma (HCC), but biomarkers of posttransplant recurrence in this setting are lacking. We evaluated the association between pretransplant plasma soluble programmed death-1 (sPD-1) and posttransplant outcomes after pretransplant ICI therapy.

Methods: We enrolled 105 HCC patients undergoing LT, including 51 receiving ICIs and 54 without prior ICI exposure. Pretransplant plasma sPD-1 and sPD-L1 were measured by ELISA. The primary endpoint was 2-year recurrence-free survival (RFS). Associations were evaluated using Kaplan–Meier analysis and Cox regression.

Results: Pretransplant sPD-1 was higher in the ICI group than in the non-ICI group (P < 0.0001). Within the ICI-treated cohort, patients who experienced recurrence had higher sPD-1 than those who did not (P = 0.0002), whereas sPD-L1 did not differ. At an internally derived exploratory cutoff of 2073 pg/mL, high sPD-1 was associated with lower 2-year RFS (7.7% vs. 76.3%; log-rank P < 0.0001; HR, 4.42; 95% CI, 1.75–11.17). As a continuous variable, each doubling of pretransplant sPD-1 was associated with an increased risk of recurrence in the unadjusted analysis (HR = 1.51, 95% CI 1.25–1.82; P < 0.001). The association remained significant after adjustment for AFP, tumor number, and maximum tumor diameter (adjusted HR = 1.51, 95% CI 1.20–1.89; P < 0.001).

Conclusion: Elevated pretransplant sPD-1 is independently associated with increased posttransplant recurrence risk in HCC patients receiving ICIs before LT. This association remained after adjustment for AFP and pretransplant tumor burden, and appeared distinct from MVI status, ACR occurrence, and the timing of blood sampling. sPD-1 may serve as a complementary biomarker for risk stratification, but external validation is required.

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Cite

BibTeXRIS
BibTeX
@article{zhu2026pretransplant,
  title = {{Pretransplant plasma soluble PD-1 and recurrence after liver transplantation in ICI-treated hepatocellular carcinoma: an exploratory biomarker study}},
  author = {Lizhen Zhu and Ruolin Wang and Wenzhi Shu and Yi Gao and Geng Zhang and Wenlong Zhao and Yucheng Hou and Qian Lu},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1944586},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1944586/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pretransplant plasma soluble PD-1 and recurrence after liver transplantation in ICI-treated hepatocellular carcinoma: an exploratory biomarker study
AU  - Lizhen Zhu
AU  - Ruolin Wang
AU  - Wenzhi Shu
AU  - Yi Gao
AU  - Geng Zhang
AU  - Wenlong Zhao
AU  - Yucheng Hou
AU  - Qian Lu
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1944586
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1944586/full
AB  - Background: Immune checkpoint inhibitors (ICIs) are increasingly used as bridging or downstaging therapy before liver transplantation (LT) for hepatocellular carcinoma (HCC), but biomarkers of posttransplant recurrence in this setting are lacking. We evaluated the association between pretransplant plasma soluble programmed death-1 (sPD-1) and posttransplant outcomes after pretransplant ICI therapy.  Methods: We enrolled 105 HCC patients undergoing LT, including 51 receiving ICIs and 54 without prior ICI exposure. Pretransplant plasma sPD-1 and sPD-L1 were measured by ELISA. The primary endpoint was 2-year recurrence-free survival (RFS). Associations were evaluated using Kaplan–Meier analysis and Cox regression.  Results: Pretransplant sPD-1 was higher in the ICI group than in the non-ICI group (P < 0.0001). Within the ICI-treated cohort, patients who experienced recurrence had higher sPD-1 than those who did not (P = 0.0002), whereas sPD-L1 did not differ. At an internally derived exploratory cutoff of 2073 pg/mL, high sPD-1 was associated with lower 2-year RFS (7.7% vs. 76.3%; log-rank P < 0.0001; HR, 4.42; 95% CI, 1.75–11.17). As a continuous variable, each doubling of pretransplant sPD-1 was associated with an increased risk of recurrence in the unadjusted analysis (HR = 1.51, 95% CI 1.25–1.82; P < 0.001). The association remained significant after adjustment for AFP, tumor number, and maximum tumor diameter (adjusted HR = 1.51, 95% CI 1.20–1.89; P < 0.001).  Conclusion: Elevated pretransplant sPD-1 is independently associated with increased posttransplant recurrence risk in HCC patients receiving ICIs before LT. This association remained after adjustment for AFP and pretransplant tumor burden, and appeared distinct from MVI status, ACR occurrence, and the timing of blood sampling. sPD-1 may serve as a complementary biomarker for risk stratification, but external validation is required.
SN  - 2234-943X
ER  -