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A high number of PD-L1+ CD14+ monocytes in peripheral blood is correlated with shorter survival in patients receiving immune checkpoint inhibitors

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Abstract

Purpose

Targeting of anti-programmed cell death protein-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) is a standard therapeutic strategy for various cancers. The aim of the present study was to investigate the prognostic effect of pretreatment PD-L1 expression levels in peripheral blood mononuclear cell (PBMC) subsets for patients with several cancer types receiving anti-PD-1 blockade therapies.

Patients and methods

Thirty-two patients undergoing anti-PD-L1 blockade therapy, including 15 with non-small cell lung cancer, 14 with gastric cancer, 1 with melanoma, 1 with parotid cancer, and 1 with bladder cancer, were recruited for the present study. PD-L1 expression levels in CD3+, CD4+, CD8+, CD45RA+ and CCR7+ T cells; CD20+ B cells; CD14+ and CD16+ monocytes were measured via flow cytometry before treatment. The percentages of PD-L1+ cells in respective PBMC subsets were compared with respect to different clinicopathological conditions and the association with overall survival (OS) was assessed.

Results

The percentages of PD-L1+ with CD3+, CD4+ and CD8+ T cells including naïve and memory T cell subsets, or CD20+ B cells during pretreatment were not markedly correlated with the OS of patients (p > 0.05); however, the percentage of the PD-L1+ CD14+ monocyte subset was significantly correlated with OS (p = 0.0426).

Conclusion

Increase in pretreatment expression levels of PD-L1 on CD14+ monocytes is associated with the OS of patients treated with immune checkpoint inhibitors. Further evaluation of large sample size and each specific cancer type might clarify the predictive role of PBMC in patients.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

No sponsor was involved.

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Authors and Affiliations

  1. Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan

    Kiyohiro Ando, Midori Shida, Ryotaro Ohkuma, Makoto Watanabe, Rie Onoue & Satoshi Wada

  2. Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan

    Kiyohiro Ando, Midori Shida, Ryotaro Ohkuma, Makoto Watanabe, Rie Onoue, Kiyoshi Yoshimura, Shinichi Kobayashi & Satoshi Wada

  3. Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Kazuyuki Hamada, Ryotaro Ohkuma, Yutaro Kubota, Atsushi Horiike, Hiroto Matsui, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Junji Tsurutani, Kiyoshi Yoshimura, Takuya Tsunoda & Satoshi Wada

  4. Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Junji Tsurutani

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  1. Kiyohiro Ando
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Contributions

KH and SW conceived and designed this study. KH, RO, YK, AH, HM, TI, YH, HA, TA, and SW collected samples and recorded the general data and patient indications. MS, MW, and RO prepared the samples. MS and RO performed all flow cytometry analyses. KA analyzed the data and wrote the first draft of the manuscript. JT, KY, TT, SK, and SW critically reviewed and revised the manuscript. All Authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Satoshi Wada.

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None of the Authors declares any conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The “Showa University Ethics Committee” approved the study with number 2165 and 2253.

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Ando, K., Hamada, K., Shida, M. et al. A high number of PD-L1+ CD14+ monocytes in peripheral blood is correlated with shorter survival in patients receiving immune checkpoint inhibitors. Cancer Immunol Immunother 70, 337–348 (2021). https://doi.org/10.1007/s00262-020-02686-6

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