Value of PD-1 and CD28 expression on T lymphocytes in predicting radiation-induced lung injury: a prospective observational study.

Abstract

Radiation-induced lung injury (RILI) remains a major dose-limiting toxicity in thoracic radiotherapy, with risk prediction relying primarily on dosimetric parameters, which show significant individual heterogeneity. This study aimed to evaluate dynamic changes in peripheral blood T-cell immune checkpoints as predictive biomarkers for ≥ Grade 2 RILI. In this prospective observational study, 274 lung cancer patients receiving thoracic radiotherapy were enrolled. Peripheral blood T-cell subsets (PD-1/CD28 expression on CD4+ and CD8+ cells) were analyzed by flow cytometry before radiotherapy (W0) and at week 2 (W2). The primary endpoint was ≥ Grade 2 RILI, assessed using CTCAE v4.0. With a median follow-up of 19 months, 87 patients (31.8%) developed ≥ Grade 2 RILI. Multivariate Cox analysis identified immunotherapy (HR=1.61, p=0.044), high mean lung dose (HR=2.33, p=0.002), and elevated levels of CD8+PD-1+ (W2, HR=2.18, p=0.030) and CD8+CD28+ (W2, HR=1.73, p=0.025) T cells as independent risk factors. Dynamic monitoring of CD8+PD-1+ and CD8+CD28+ T cells early during radiotherapy provides a novel and independent biological indicator for predicting RILI risk, complementing traditional dosimetric assessment.