von der Gruen, Jens, Winkelmann, Ria, Meissner, Markus, Wieland, Ulrike, Silling, Steffi, Martin, Daniel, Fokas, Emmanouil, Roedel, Claus, Roedel, Franz and Balermpas, Panagiotis ORCID: 0000-0001-5261-6446 (2019). Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma. Front. Oncol., 9. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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Abstract

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 immunemarker 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
von der Gruen, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkelmann, RiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meissner, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wieland, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silling, SteffiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fokas, EmmanouilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roedel, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roedel, FranzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balermpas, PanagiotisUNSPECIFIEDorcid.org/0000-0001-5261-6446UNSPECIFIED
URN: urn:nbn:de:hbz:38-158934
DOI: 10.3389/fonc.2019.00020
Journal or Publication Title: Front. Oncol.
Volume: 9
Date: 2019
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 2234-943X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LARGE T-ANTIGEN; RADIATION-THERAPY; INDEPENDENT PREDICTOR; CHECKPOINT BLOCKADE; PROGNOSTIC-FACTORS; NECK-CANCER; INFECTION; MULTICENTER; HEAD; CHEMORADIOTHERAPYMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15893

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