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Longitudinal immunophenotyping identifies early postoperative CD8-positive PD-1-positive T cells as an independent predictor of 1-year mortality after lung transplantation

Presenter
Tianyi Yang (CN)

Shanghai Pulmonary Hospital · Shanghai

Profile

Authors

Tianyi Yang1,2,3, Peigen Gao1,2,3, Guodong Wu1,2,3, Yingjian Liu1,2,3, Haoxuan Liu1,2,3, Lang Xia1,3, Lei Zhang1,3, Yichen Wang1,3, Yanfeng Zhao1,3, Chang Chen1,2,3, Junqi Wu1,2,3

Affiliations

1 Shanghai pulmonary hospital
2 Shanghai pulmonary hospital
3 Tongji University

Abstract

Introduction: Early postoperative mortality following lung transplantation (LTx) remains a significant clinical challenge. Patients who survive the first year have markedly better long‑term outcomes. We aimed to evaluate whether early postoperative T-cell immunophenotypes are associated with 1-year overall survival.
Methods: This prospective cohort study included LTx recipients undergoing serial peripheral blood flow cytometric assessments during the first 3 months postoperatively. Elastic net (EN) regularization and univariate Cox regression were applied for feature selection. Multivariable Cox regression and restricted mean survival time difference (RMSTd) analyses were used to evaluate associations with 1-year mortality.
Results: We evaluated 48 patients with 226 flow cytometric assessments, including 184 samples from the first postoperative month and 42 samples at 2–3 months

Figure 1
Distinct early postoperative T-cell immunophenotypes. (A) Study design. (B-C) Unsupervised hierarchical clustering and characterization of these immune profiles. (D-E) Association of T-cell clusters with 1-year overall survival.
. The 1-year overall mortality was 29.2% (14/48). EN regularization and multivariable analysis consistently identified the mean proportion of CD8⁺ PD-1⁺ T cells within the first month as the strongest predictor of 1-year mortality (adjusted HR: 1.43 per 10% increase, 95% CI: 1.06–1.93; p=0.019). Utilizing a median cutoff of 41.2%, patients in the high CD8⁺ PD-1⁺ T-cell group exhibited significantly inferior 1-year overall survival compared with the low group (1-year mortality: 45.8% vs. 12.5%; p=0.018), with a marked reduction in RMSTd of -62.5 days (95% CI: -120.8 to -4.2; p=0.036). Notably, 72.7% (8/11) of deaths in the high CD8⁺ PD-1⁺ T-cell group were infection-related. Persistently elevated CD8⁺ PD-1⁺ T cells at 2–3 months provided incremental prognostic discrimination
Figure 2
Prognostic significance of CD8⁺ PD-1⁺ T cells. (A) Feature selection via elastic net regularization. (B) Flow cytometry gating strategy. (C) Kaplan-Meier curves stratified by the median proportion of CD8⁺ PD-1⁺ T cells. (D) Longitudinal trajectories linking early dynamics to clinical outcomes.
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Conclusion: Early expansion of circulating CD8⁺ PD-1⁺ T cells is strongly associated with an increased risk of 1-year mortality, particularly infection-related death. Dynamic monitoring of this immunophenotype may enable individualized risk stratification and guide post-transplant management.