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Circulating PD-L1 is associated with T cell infiltration and predicts prognosis in patients with CRLM following hepatic resection

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Abstract

Background

Exosomal PD-L1 (exoPD-L1) could induce immunosuppression functionally, thus impairing patients’ survival in melanoma, NSCLC, and gastric cancer. However, no evidence demonstrates the feasibility of circulating exoPD-L1 and soluble PD-L1 (sPD-L1) as biomarkers for prognosis and early recurrence in colorectal liver metastasis (CRLM) patients following hepatectomy or their association with T cell infiltration at liver metastases.

Methods

In cohort 1, exoPD-L1 and sPD-L1 were preoperatively tested using ELISA. CD3, CD8, granzyme B (GB) and PD1 expressed at liver metastases were evaluated using immunohistochemistry. In cohort 2, exoPD-L1 and sPD-L1 were detected at baseline, before hepatectomy, after hepatectomy, and after disease progression.

Results

In cohort 1, higher preoperative exoPD-L1 or sPD-L1 significantly impaired RFS (exoPD-L1, P = 0.0043; sPD-L1, P = 0.0041) and OS (exoPD-L1, P = 0.0034; sPD-L1, P = 0.0061). Furthermore, preoperative exoPD-L1 was negatively correlated with CD3 + T-lymphocytes infiltrated at tumor center (CT), and GB and PD1 were expressed at tumor invasive margin (IM). Preoperative sPD-L1 was negatively correlated with CD3 + and CD8 + T-lymphocytes’ infiltration at IM and CT, GB and PD1 expression at IM. In cohort 2, exoPD-L1 and sPD-L1 levels decreased following hepatectomy but increased when tumor progressed. Moreover, higher postoperative exoPD-L1 and sPD-L1 or a small reduction in exoPD-L1 and sPD-L1 levels after hepatectomy suggested higher early recurrence rate.

Conclusions

Both preoperative exoPD-L1 and sPD-L1 had promising prognostic values and were associated with T cell infiltration at liver metastases in CRLM patients following hepatectomy. Dynamically tracking exoPD-L1 and sPD-L1 levels could monitor disease status and detect early recurrence.

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Funding

This work was supported by the National Natural Science Foundation of China (81872010).

Author information

Author notes

  1. Xiuxing Chen, Ziming Du and Mayan Huang have contributed equally.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651# Dongfeng Road East, Guangzhou, 510060, People’s Republic of China

    Xiuxing Chen, Ziming Du, Mayan Huang, Deshen Wang, William Pat Fong, Jieying Liang, Yun Wang, Hui Yang, Zhigang Chen, Mingtao Hu, Ruihua Xu & Yuhong Li

  2. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China

    Xiuxing Chen, Deshen Wang, William Pat Fong, Jieying Liang, Hui Yang, Zhigang Chen, Mingtao Hu, Ruihua Xu & Yuhong Li

  3. Department of Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China

    Xiuxing Chen

  4. Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People’s Republic of China

    Ziming Du

  5. Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China

    Ziming Du

  6. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China

    Mayan Huang

  7. School of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, People’s Republic of China

    Lei Fan

  8. Department of Hematologic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China

    Yun Wang

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  1. Xiuxing Chen
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Correspondence to Ruihua Xu or Yuhong Li.

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All access to blood samples and clinical data for research was approved by the institutional review board and ethics committee of Sun Yat-sen University Cancer Center (B2020-018–01).

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Chen, X., Du, Z., Huang, M. et al. Circulating PD-L1 is associated with T cell infiltration and predicts prognosis in patients with CRLM following hepatic resection. Cancer Immunol Immunother 71, 661–674 (2022). https://doi.org/10.1007/s00262-021-03021-3

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  • DOI: https://doi.org/10.1007/s00262-021-03021-3

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