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Front. Oncol. | doi: 10.3389/fonc.2019.00020

Merkel cell polyoma viral load and intratumoral CD8+ lymphocyte infiltration predict overall survival in patients with Merkel cell carcinoma

 Jens von der Grün1, Ria Winkelmann1,  Markus Meissner1, Ulrike Wieland2, Steffi Silling2, Daniel Martin1,  Emmanouil Fokas1, 3, 4, Claus M. Rödel1, 3, 4,  Franz Rödel1, 3, 4 and  Panagiotis Balermpas1, 3, 4, 5*
  • 1Department of Radiation Oncology, Goethe-Universität Frankfurt am Main, Germany
  • 2Institute of Virology, National Reference Center for Papilloma‐ and Polyomaviruses, Universität zu Köln, Germany
  • 3German Cancer Consortium, German Cancer Research Center (DKFZ), Germany
  • 4Partner site Frankfurt am Main, German Cancer Consortium (DKTK), Germany
  • 5Department of Radiation Oncology, University Hospital Zürich, Switzerland

Introduction: Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration.
Methods: MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with (n=22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS).
Results: Median age at diagnosis was 74 (range, 42-100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8%, 58.6% and 47.1%, respectively. A positive MCPyV status was associated with female gender (p=0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (p=0.011) and combined CD8/PD-L1 expression (p=0.038). Overall CD8+ infiltration was inversely associated with N-stage (p=0.048). Stromal TILs correlated significantly with both PD-L1 expression (p=0.010) and N-stage (p=0.037). A high viral load (>median) was significantly associated with worse OS (p=0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (p=0.045).
Conclusion: These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.

Keywords: merkel cell carcinoma, polyomavirus (MCPyV), CD8+ tumor infiltrating lymphocytes, PD-L1, radioimmunotherpay

Received: 19 Oct 2018; Accepted: 07 Jan 2019.

Edited by:

Peter Brossart, Universität Bonn, Germany

Reviewed by:

Graham R. Leggatt, The University of Queensland, Australia
Daniel Olive, Faculté de Médecine, Aix Marseille Université, France  

Copyright: © 2019 von der Grün, Winkelmann, Meissner, Wieland, Silling, Martin, Fokas, Rödel, Rödel and Balermpas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Panagiotis Balermpas, Goethe-Universität Frankfurt am Main, Department of Radiation Oncology, Frankfurt, 60325, Hesse, Germany, Panagiotis.balermpas@usz.ch