AUTHOR=von der Grün Jens , Winkelmann Ria , Meissner Markus , Wieland Ulrike , Silling Steffi , Martin Daniel , Fokas Emmanouil , Rödel Claus , Rödel Franz , Balermpas Panagiotis 

TITLE=Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00020

DOI=10.3389/fonc.2019.00020

ISSN=2234-943X

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 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).</p><p><bold>Results:</bold> 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 (<italic>p</italic> = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status (<italic>p</italic> = 0.011) and combined CD8/PD-L1 expression (<italic>p</italic> = 0.038). Overall CD8+ infiltration was inversely associated with N-stage (<italic>p</italic> = 0.048). Stromal TILs correlated significantly with both PD-L1 expression (<italic>p</italic> = 0.010) and N-stage (<italic>p</italic> = 0.037). A high viral load (&gt;median) was significantly associated with worse OS (<italic>p</italic> = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort (<italic>p</italic> = 0.045).</p><p><bold>Conclusion:</bold> 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.</p>