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Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy

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Abstract

Purpose

Chemokines influence both tumor progression and anti-tumor immune response. A 32-bp-deletion polymorphism in the chemokine receptor 5 gene (CCR5Δ32) has been shown to result in a non-functional protein. This study was aimed at evaluating the potential impact of this gene polymorphism on disease progression and treatment outcome in patients with melanoma.

Patients and methods

CCR5 genotyping was performed by PCR on DNA extracted from serum samples of 782 cutaneous melanoma patients with known disease history and long-term clinical follow-up. Genotypes were correlated with patient survival and types of treatment.

Results

Of 782 melanoma patients, 90 (11.5%) were heterozygous and 12 (1.5%) were homozygous for CCR5Δ32. Analyzing the complete cohort, the disease-specific survival from date of primary diagnosis was not influenced by CCR5 status. Similarly, no significant impact could be detected on the treatment outcome of stage III patients. In 139 stage IV patients receiving immunotherapy, CCR5Δ32 was associated with a decreased survival compared to patients not carrying the deletion (median 12.5 vs. 20.3 months, P = 0.029). Multivariate analysis revealed the CCR5 genotype as an independent factor impacting disease-specific survival in this patient population (P = 0.002), followed by gender (P = 0.019) and pathological classification of the primary (pT; P = 0.022).

Conclusion

The presence of the CCR5Δ32 polymorphism in patients with stage IV melanoma results in a decreased survival following immunotherapy and may help to select patients less likely to benefit from this type of treatment.

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Acknowledgments

Grant support: This study was supported by the Wilhelm Sander Stiftung (# 2006.054.1).

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Authors and Affiliations

  1. Department of Dermatology, Julius-Maximilians University, Würzburg, Germany

    Selma Ugurel, David Schrama, Gunhild Keller, Eva-Bettina Bröcker, Roland Houben & Jürgen C. Becker

  2. Skin Cancer Unit, German Cancer Research Center Heidelberg/Department of Dermatology, University Hospital Mannheim, Mannheim, Germany

    Dirk Schadendorf & Wolfram Fink

  3. Department of Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany

    Marc Zapatka

  4. Division of Surgical Oncology, College of Physicians and Surgeons, Columbia University Medical Center, New York, USA

    Howard L. Kaufman

  5. Department of Dermatology, University of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany

    Jürgen C. Becker

Authors
  1. Selma Ugurel
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  2. David Schrama
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  3. Gunhild Keller
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  4. Dirk Schadendorf
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  5. Eva-Bettina Bröcker
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  6. Roland Houben
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  7. Marc Zapatka
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  8. Wolfram Fink
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  9. Howard L. Kaufman
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  10. Jürgen C. Becker
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Corresponding author

Correspondence to Jürgen C. Becker.

Additional information

Selma Ugurel and David Schrama have contributed equally to this work.

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Ugurel, S., Schrama, D., Keller, G. et al. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother 57, 685–691 (2008). https://doi.org/10.1007/s00262-007-0407-z

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  • DOI: https://doi.org/10.1007/s00262-007-0407-z

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