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 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.
Highlights
Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases
Future clinical studies should aim to explore the effect of PD-1/programmed death ligand 1 (PD-L1) immune-checkpoint inhibitors in combination with existing radiotherapy approaches
We quantitatively evaluated the prevalence, viral load, and genomic integration into the host DNA of MCPyV in a cohort of MCC-patients and correlated these parameters with overall survival (OS), PD-L1 status, and CD8+ lymphocyte infiltration
Summary
Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with an incidence rate of 0.13 per 1,00,000 residents in Europe between 1995 and 2002 [1]. MCC tumorigenesis is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases, or mutagenesis from ultraviolet light (UV) exposure for MCPyV-negative tumors, as well as advanced age and immunosuppression [3, 7]. MCPyV integrates into the host cells genome and persistent expression of MCPyV T antigens is required for MCC tumor cell survival [8]. Immunosuppression due to, e.g., organ transplantation or chronic lymphatic leukemia significantly increases the risk for MCC, indicating a pivotal role of the host immune system in tumorigenesis [7]
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