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Chemokine level predicts the therapeutic effect of anti-PD-1 antibody (nivolumab) therapy for malignant melanoma

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Abstract

Anti-programmed cell death protein 1 (PD-1) antibody drugs, nivolumab and pembrolizumab, are regarded as first-line therapies for advanced malignant melanoma. Anti-PD-1 therapy suppresses tumor immunity, and the therapeutic effect is frequently correlated with the number of tumor-infiltrating lymphocytes (TIL) and tumor mutation burden (TMB). However, sampling tumor tissues from the metastatic sites to examine the number of TILs and TMB level is often challenging. Herein, we focused on chemokines in blood to determine whether they can predict the therapeutic effect of anti-PD-1 (nivolumab) therapy. First, we measured 44 types of chemokines and cytokines in the blood of 8 advanced malignant melanomas before anti-PD-1 (nivolumab) treatment and examined the relationship between the levels of these proteins and therapeutic effect of the drug treatment, which suggested that C–C motif chemokine 5 (CCL5) and C–X–C motif chemokine ligand 12 (CXCL12) were candidates for biomarkers to predict the therapeutic effect of anti-PD-1 therapy. Next, we measured the blood levels of CCL5 and CXCL12 in 22 patients with advanced malignant melanomas before the administration of anti-PD-1 antibody. We evaluated tumor infiltration of CD8-positive T cells by immunostaining in nine patients in whom the metastatic site could be sampled at the beginning of the treatment. The patients with lower than average levels of CCL5 and CXCL12 had a large number of TILs (P = 0.04) and good disease-specific survival rate (P = 0.04). Therefore, CCL5 and CXCL12 could likely be used as biomarkers to predict the therapeutic effect of anti-PD-1 (nivolumab) therapy.

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Availability of data and material

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Ms. Aya Uchiyama for the technical assistance.

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Authors and Affiliations

  1. Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Kenta Nakamura, Atsuko Ashida, Yukiko Kiniwa & Ryuhei Okuyama

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  1. Kenta Nakamura
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  2. Atsuko Ashida
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  3. Yukiko Kiniwa
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  4. Ryuhei Okuyama
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Contributions

KN conceived, designed, and performed the experiments; analyzed the data; and wrote the manuscript. AA, YK, and RO conceived and designed the experiments and wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Kenta Nakamura.

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The authors declare the following financial interests/personal relationships which may be considered as potential competing interests.

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The protocol for this human study was approved by the ethics committee of Shinshu University Graduate School of Medicine, Matsumoto, Japan (Permit No: 569).

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Nakamura, K., Ashida, A., Kiniwa, Y. et al. Chemokine level predicts the therapeutic effect of anti-PD-1 antibody (nivolumab) therapy for malignant melanoma. Arch Dermatol Res 314, 887–895 (2022). https://doi.org/10.1007/s00403-021-02305-z

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  • DOI: https://doi.org/10.1007/s00403-021-02305-z

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