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Efficacy relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy

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Abstract

Purpose

Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predicting and stratifying metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy.

Methods

Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high).

Results

Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P = 0.033) and OS (P = 0.00058) compared with patients with a cut-off value of < 35% PD-L1-high CTCs.

Conclusion

Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy.

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Data availability

All data are available within the manuscript or may be obtained from the corresponding authors upon reasonable request.

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Funding

This work was supported by grants from Research Foundation for Advanced Talents of Fujian Medical University (XRCZX2017020, XRCZX2019005), Beijing Natural Science Foundation (7192198), Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000, XDB38010400), the National Natural Science Foundation of China (32027801, 31870992, 21775031), the Natural Science Foundation of Fujian Province (2022J01203), CAS-JSPS (GJHZ2094), Science and Technology Service Network Initiative of the Chinese Academy of Sciences (KFJ-STS-ZDTP-079).

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Author notes

  1. Ying Zhou, Jinmei Zhou, Xiaopeng Hao and Haoyuan Shi have contributed equally to this work.

Authors and Affiliations

  1. Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China

    Ying Zhou, Haoyuan Shi, Xuejie Li, Anqi Wang & Zhiyuan Hu

  2. CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China

    Ying Zhou, Haoyuan Shi, Xuejie Li, Anqi Wang, Zhiyuan Hu & Yanlian Yang

  3. Breast Cancer Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

    Jinmei Zhou, Zefei Jiang & Tao Wang

  4. Department of General Surgery, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

    Xiaopeng Hao

  5. School of Nanoscience and Technology, Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China

    Zhiyuan Hu & Yanlian Yang

  6. School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China

    Zhiyuan Hu

  7. Anhui Medical University, Hefei, China

    Tao Wang

  8. Southern Medical University, Guangzhou, China

    Tao Wang

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Contributions

TW, ZJ, YY, and ZH contributed to the study conception and design. Material preparation, data collection and analysis were performed by YZ, JZ, XH, HS, XL, and AW. The first draft of the manuscript was written by YZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhiyuan Hu, Yanlian Yang, Zefei Jiang or Tao Wang.

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Zhou, Y., Zhou, J., Hao, X. et al. Efficacy relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy. Breast Cancer Res Treat 200, 281–291 (2023). https://doi.org/10.1007/s10549-023-06972-6

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