Peripheral regulatory T cells trajectory predicts progression-free survival in hepatocellular carcinoma patients
Qiyang Chen1, Siwei Yang2, Jian Li3
1Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background:
Regulatory T cells (Tregs) can be regulated by transarterial chemoembolization (TACE). However, the dynamic changes in Tregs during on-demand TACE remain unclear. This study aimed to investigate the prognostic value of longitudinal Tregs trajectory in patients with unresectable hepatocellular carcinoma (HCC) who underwent on-demand TACE.
Methods:
This prospective study included consecutive treatment-naive HCC patients who met the inclusion criteria from March to December 2024. Peripheral Tregs was measured at baseline and multiple follow-up timepoints during on-demand TACE. A joint model of a linear mixed sub-model and Cox proportional hazards sub-model was constructed to estimate the impact of longitudinal Treg trajectory on progression-free survival (PFS).
Results:
There were 30 HCC patients with 109 Treg measurements included. During a median follow-up of 13.3 [interquartile range (IQR), 10.8-15.3] months, progressive disease (PD) was observed in 11 patients. Time was identified as the sole factor influencing Tregs trajectory. Tregs at T3 (9-16 weeks after initial TACE or 1 day before third TACE if necessary) were lower than those at T0 (1 day before initial TACE) [5.84 (IQR, 4.97-8.40) vs. 6.96 (IQR, 5.28-10.37), P=0.007]. A decreasing trend was observed between Tregs at T2 (4-8 weeks after initial TACE) and T0 (P=0.057). No significant differences were observed between Tregs at T1 (within 1 week after the initial TACE) and other timepoints. In the joint model, the trajectory of Tregs and Barcelona Clinic Liver Cancer (BCLC) stage were predictors for PFS. For each 1% increase in the Tregs, the hazard ratio (HR) of PD was 2.04 [95% confidence interval (CI): 1.31-3.92; P<0.001]. Compared with BCLC A, BCLC B was associated with higher PD risk (HR: 3.80, 95% CI: 1.55-8.06; P=0.02).
Conclusions:
Longitudinal trajectory of peripheral Tregs independently predicted PFS of HCC patients who underwent on-demand TACE. Dynamically monitoring Tregs holds promise for guiding the timing of the therapy strategy.
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