TY  - JOUR
A1  - Müller-von der Grün, Jens
A1  - Winkelmann, Anne Ria
A1  - Meissner, Markus
A1  - Wieland, Ulrike
A1  - Silling, Steffi
A1  - Martin, Daniel
A1  - Fokas, Emmanouil
A1  - Rödel, Claus
A1  - Rödel, Franz
A1  - Balermpas, Panagiotis
T1  - Merkel cell polyoma viral load and intratumoral CD8+ lymphocyte infiltration predict overall survival in patients with Merkel cell carcinoma
T2  - Frontiers in oncology
N2  - 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.
KW  - merkel cell carcinoma
KW  - polyomavirus (MCPyV)
KW  - CD8+ tumor infiltrating lymphocytes
KW  - PD-L1
KW  - radioimmunotherpay
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49084
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-490847
SN  - 2234-943X
N1  - 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.
VL  - 9
IS  - Art. 20
SP  - 1
EP  - 8
PB  - Frontiers Media
CY  - Lausanne
ER  -