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Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

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Abstract

Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project ‘Immune Modulating strategies for treatment of Merkel Cell Carcinoma’, which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.

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Abbreviations

HDAC:

Histone deacetylase

ICD-O:

International Classification of Diseases for Oncology

IMMOMEC:

Immune Modulating Strategies for Treatment of Merkel Cell Carcinoma

LT:

Large T-antigen

MAX:

Myc-associated factor X

MCC:

Merkel cell carcinoma

MCPyV:

Merkel cell polyomavirus

MDM2:

Mouse double minute 2 homolog

MHC:

Major histocompatibility complex

MIC:

MHC class I chain-related protein

MYCL:

l-Myc-1 proto-oncogene protein

NKG2D:

Natural killer group 2D

PD-1:

Programmed death protein 1

PD-L1:

Programmed death-ligand 1

PP:

Pocket protein

RB:

Retinoblastoma protein

sT:

Small T-Antigen

TIL:

Tumor-infiltrating lymphocytes

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Authors and Affiliations

  1. Translational Skin Cancer Research (tscr), German Cancer Consortium (DKTK), University Hospital of Essen, Universitätsstrasse 1, S05 T05 B, 45141, Essen, Germany

    Jürgen C. Becker & Cathrin Ritter

  2. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Jürgen C. Becker, Andreas Stang & Cathrin Ritter

  3. Center of Clinical Epidemiology; c/o Institute of Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany

    Andreas Stang

  4. Department of Pathology, Academisch Ziekenhuis Maastricht, Maastricht, The Netherlands

    Axel zur Hausen

  5. Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Nicole Fischer

  6. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    James A. DeCaprio

  7. Peter McCallum Cancer Centre, Melbourne, Australia

    Richard W. Tothill

  8. Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Copenhagen, Denmark

    Rikke Lyngaa

  9. George F. Odland Endowed Chair in Dermatology, University of Washington, Seattle, WA, USA

    Ulla Kring Hansen & Paul Nghiem

  10. University of Michigan Medical School, Ann Arbor, MI, USA

    Christopher K. Bichakjian

  11. Department of Dermatology, University Hospital of Essen, Essen, Germany

    Jürgen C. Becker & Selma Ugurel

  12. Department of Dermatology, University Hospital Wuerzburg, Würzburg, Germany

    David Schrama

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  1. Jürgen C. Becker
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Correspondence to Jürgen C. Becker.

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Funding

J. C. Becker is funded by the European Commission Grant Agreement #277,775/IMMOMEC, the BMBF 03VP01062/CTCelect, the Hiege Stiftung, and the German Cancer Consortium (DKTK). A. Stang receives a Grant from the German Federal Ministry of Education and Science (BMBF), Grant Number 01ER1305. J. A. DeCaprio was supported in part by US Public Health Service Grants R01CA63113, R01CA173023, P01CA050661, the DFCI Helen Pappas Merkel Cell Research Fund and the Claudia Adams Barr Program in Cancer Research. P. Nghiem was supported in part by US Public Health Service grants K24-CA139052, RO1-CA176841, and the UW MCC Gift Fund.

Conflict of interest

J. C. Becker has received speaker honoraria from Amgen, MerckSerono, and Pfizer, advisory board honoraria from Amgen, CureVac, eTheRNA, Lytix, MerckSerono, Novartis, Rigontec, and Takeda as well as research funding from Boehringer Ingelheim, BMS and MerckSerono; the activities with BMS, MerckSerono and Pfizer are related to the submitted report (therapy of advanced MCC). A research project in J. A. DeCaprio’s laboratory is supported by Constellation Pharmaceuticals. P. Nghiem has served as a consultant for EMD Serono and Pfizer and has received research support to his institution from Bristol-Myers Squibb. The other authors declare that they have no conflict of interest.

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Becker, J.C., Stang, A., Hausen, A.z. et al. Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC. Cancer Immunol Immunother 67, 341–351 (2018). https://doi.org/10.1007/s00262-017-2099-3

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