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Co-expression of NGF and PD-L1 on tumor-associated immune cells in the microenvironment of Merkel cell carcinoma

Abstract

Purpose

Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor with known viral association. The microenvironment and its interaction with the tumor via the programmed cell death protein 1 (PD-1) pathway are crucial for response to anti-PD-1/anti-PD-L1 treatments. However, not all patients respond, which is suggestive of additional mechanisms for tumor growth and/or persistence. We previously detected tropomyosin receptor kinase A (TrkA) expression on MCC tumor cells and, therefore, gained interest in the expression of its ligand nerve growth factor (NGF).

Methods

Thirty-nine patients from our department were studied for immunohistochemical NGF, PD-1, and PD-L1 expression and clinico-pathological correlation.

Results

PD-L1 was expressed on the tumor cells in 42%. In 95%, PD-L1 expression was also found on CD68+ spindle cells at the tumor border, which co-expressed NGF in 71%. 66% contained PD-1+ tumor infiltrating lymphocytes. PD-1, PD-L1, and NGF expression seems to correlate with a worse outcome.

Conclusions

The present study shows that PD-L1 and NGF are co-expressed on spindle cells in the microenvironment. The expression of NGF might be a link of the microenvironment to the TrkA-positive tumor cells. Whether this mechanism is critical for tumor growth and lack of response to anti-PD-1/L1 treatment has to be investigated in further studies.

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Acknowledgements

The authors thank Hans-Michael Behrens and Thomas Langkamp for advice regarding statistical calculations and Arne Voss for help in image editing.

Funding

None.

Author information

Correspondence to Ulrike Wehkamp.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Wehkamp, U., Stern, S., Krüger, S. et al. Co-expression of NGF and PD-L1 on tumor-associated immune cells in the microenvironment of Merkel cell carcinoma. J Cancer Res Clin Oncol 144, 1301–1308 (2018). https://doi.org/10.1007/s00432-018-2657-x

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Keywords

  • NGF
  • Merkel cell carcinoma
  • PD-L1
  • PD-1
  • TrkA