{
  "abstract": "Purpose This study was conducted to assess the clinical significance of programmed cell death-ligand 1 (PD-L1)-positive circulating tumor cells (CTCs) as predictive biomarkers for the efficacy of PD-(L)1 inhibitor-based treatment in advanced hepatocellular carcinoma (HCC).Experimental design We enrolled 59 patients with unresectable HCC who received immunotherapy-based treatment and analyzed CTCs, PD-L1 +CTCs and molecules in peripheral blood. An innovative telomerase reverse transcriptase-based method was applied to detect specific CTCs. Kaplan-Meier analysis and Cox regression were used to evaluate clinical outcomes, such as progression-free survival (PFS) and overall survival (OS).Results CTCs were detected in 86.4% (51/59) of patients, with a PD-L1-positive rate of 83.7% (41/49). Compared with the “PD-L1 +CTC Low” group, the “PD-L1+CTC High” group had significantly shorter PFS (median PFS: 7.72 vs 16.1 months, p=0.037) and shorter OS (median OS: 13.89 vs 36.97 months, p=0.031). The “PD-L1+CTC Fewer & Low” group had the longest survival outcomes (median PFS: 17.03 months, median OS: 36.97 months), whereas the “PD-L1+CTC More & High” group had the poorest outcomes (median PFS: 5.3 months, median OS: 10.77 months) (p<0.05). Multivariate analysis revealed that the PD-L1+CTC count and ratio were an independent predictor of PFS. Significant correlations were found between PD-L1+CTC and several immune-related molecules, such as immune checkpoint molecules (CD28, TIM-3, and CD80) and regulatory factors (BDNF, and BLTA).Conclusions PD-L1 +CTCs are potential indicators correlating with the shorter PFS and OS of immunotherapy-based treatment in patients with advanced HCC. The “PD-L1+CTC Low & Fewer” classification was associated with better clinical outcomes and immune-related molecules.",
  "authors": [
    {
      "affiliations": [
        "Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Caifeng Gong"
    },
    {
      "affiliations": [
        "Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Shuhui You"
    },
    {
      "affiliations": [
        "State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Department of Gastroenterology, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China"
      ],
      "name": "Qi Zhang"
    },
    {
      "affiliations": [
        "Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Beijing Key Laboratory of Cell and Gene Therapy for Digestive System Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"
      ],
      "name": "Zhenrong Yang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Xinyu Bi"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Hong Zhao"
    },
    {
      "affiliations": [
        "Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Yongkun Sun"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Jianguo Zhou"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Weiqi Rong"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Jianjun Zhao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Kaitai Zhang"
    },
    {
      "affiliations": [
        "Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Aiping Zhou"
    },
    {
      "affiliations": [
        "Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Beijing Key Laboratory of Cell and Gene Therapy for Digestive System Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Wen Zhang"
    },
    {
      "affiliations": [
        "Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Wen Zhang"
    }
  ],
  "title": "PD-L1 expression on circulating tumor cells for predicting clinical outcomes in patients with hepatocellular carcinoma receiving PD-(L)1 blockade and targeted therapy",
  "uid": "7657a97c-67fb-5e3f-9c87-47258466af6b"
}