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Serum PD-1 Levels Change with Immunotherapy Response but Do Not Predict Prognosis in Patients with Hepatocellular Carcinoma

대한간암학회지 2019년 19권 2호 p.108 ~ 116
 ( Lee Hye-Won ) - Yonsei University College of Medicine Department of Internal Medicine

조경주 ( Cho Kyung-Joo ) - Yonsei University College of Medicine Department of Internal Medicine
신순영 ( Shin Soon-Young ) - Yonsei University College of Medicine Department of Internal Medicine
 ( Kim Ha-Yan ) - Yonsei University College of Medicine Biostatistics Collaboration Unit
이은주 ( Lee Eun-Ju ) - Yonsei University College of Medicine Biostatistics Collaboration Unit
김범경 ( Kim Beom-Kyung ) - Yonsei University College of Medicine Department of Internal Medicine
 ( Kim Seung-Up ) - Yonsei University College of Medicine Department of Internal Medicine
박준용 ( Park Jun-Yong ) - Yonsei University College of Medicine Department of Internal Medicine
김도영 ( Kim Do-Young ) - Yonsei University College of Medicine Department of Internal Medicine
 ( Ahn Sang-Hoon ) - Yonsei University College of Medicine Department of Internal Medicine
 ( Han Kwang-Hyub ) - Yonsei University College of Medicine Department of Internal Medicine

Abstract


Background/Aims: Programmed death receptor 1 (PD-1) is a promising new target for treatment of patients with hepatocellular carcinoma (HCC). A high expression level of programmed death-ligand 1 (PD-L1) is a possible prognostic indicator for poor outcome in other malignancies. Here, we investigated the clinical significance of PD-1 and PD-L1 in patients with HCC.

Methods: We enrolled patients with HCC who underwent surgical resection at Severance Hospital between 2012 and 2017 and investigated the levels of PD-L1 in HCC tissues (tPD-L1) and PD-L1/PD-1 in serum (sPD-L1/sPD-1). We also aimed to determine whether expression levels correlated with clinical and histological features.

Results: A total of 72 patient samples were analyzed. The median sPD-L1 and sPD-1 levels were 25.72 and 341.44 pg/mL, respectively. A positive correlation was detected between tPD-L1 and sPD-1 levels (R2=0.426, P<0.001). The median sPD-1 level increased linearly with tPD-L1 score (P=0.002). During the follow-up period, HCC recurred in eight (11.1%) patients and liver-related mortality occurred in eight (11.1%) patients. Higher sPD-L1 levels (≥19.18 pg/mL) tended to be associated with liver-related mortality (hazard ratio 6.866; 95% confidence interval, 0.804-58.659, P=0.078). sPD-1 levels of patients treated with nivolumab as a second-line therapy changed serially, and a >50% reduction in sPD-1 levels was observed immediately after nivolumab administration. However, sPD-1 level was not associated directly with prognosis in patients with advanced HCC.

Conclusions: The results demonstrated that PD-L1 and PD-1 levels changed according to the immunotherapy. However, no significant association with clinical outcome in patients with HCC was detected.

키워드

Programmed death-ligand 1; Programmed death receptor 1; Prognosis; Hepatocellular carcinoma
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