Universität zu Köln

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:	Creators Email ORCID ORCID Put Code von der Gruen, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkelmann, Ria UNSPECIFIED UNSPECIFIED UNSPECIFIED Meissner, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieland, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Silling, Steffi UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Fokas, Emmanouil UNSPECIFIED UNSPECIFIED UNSPECIFIED Roedel, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Roedel, Franz UNSPECIFIED UNSPECIFIED UNSPECIFIED Balermpas, Panagiotis UNSPECIFIED orcid.org/0000-0001-5261-6446 UNSPECIFIED
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:	Keywords Language LARGE T-ANTIGEN; RADIATION-THERAPY; INDEPENDENT PREDICTOR; CHECKPOINT BLOCKADE; PROGNOSTIC-FACTORS; NECK-CANCER; INFECTION; MULTICENTER; HEAD; CHEMORADIOTHERAPY Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15893