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Updated: May 4, 2026
Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell
Evan J Lipson1, Jeremy G Vincent2, Myriam Loyo3
1Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21287.
Abstract:
Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have demonstrated objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression in the tumor microenvironment. To investigate whether MCC might be a target for PD-1/PD-L1 blockade, we examined MCC PD-L1 expression, its association with tumor-infiltrating lymphocytes (TILs), Merkel cell polyomavirus (MCPyV), and overall survival. Sixty-seven MCC specimens from 49 patients were assessed with immunohistochemistry for PD-L1 expression by tumor cells and TILs, and immune infiltrates were characterized phenotypically. Tumor cell and TIL PD-L1 expression were observed in 49% and 55% of patients, respectively. In specimens with PD-L1(+) tumor cells, 97% (28/29) demonstrated a geographic association with immune infiltrates. Among specimens with moderate-severe TIL intensities, 100% (29/29) demonstrated PD-L1 expression by tumor cells. Significant associations were also observed between the presence of MCPyV DNA, a brisk inflammatory response, and tumor cell PD-L1 expression: MCPyV(-) tumor cells were uniformly PD-L1(-). Taken together, these findings suggest that a local tumor-specific and potentially MCPyV-specific immune response drives tumor PD-L1 expression, similar to previous observations in melanoma and head and neck squamous cell carcinomas. In multivariate analyses, PD-L1(-) MCCs were independently associated with worse overall survival (hazard ratio 3.12; 95% CI, 1.28-7.61; p=0.012). These findings suggest that an endogenous immune response promotes PD-L1 expression in the MCC microenvironment when MCPyV is present, and provide a rationale for investigating therapies blocking PD-1/PD-L1 for patients with MCC.
Insights
Merkel cell carcinoma (MCC) shows PD-L1 expression linked to the virus and immune cells. PD-L1 negative MCC is associated with worse survival, suggesting PD-1/PD-L1 blockade therapy potential.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Merkel cell carcinoma (MCC) is an aggressive skin cancer with limited treatment options for advanced stages.
- Immuno-oncology agents targeting the PD-1/PD-L1 pathway show promise in various advanced cancers.
- PD-L1 expression in the tumor microenvironment is a biomarker for response to PD-1/PD-L1 blockade.
Purpose of the Study:
- To investigate PD-L1 expression in MCC.
- To assess the association of PD-L1 expression with tumor-infiltrating lymphocytes (TILs), Merkel cell polyomavirus (MCPyV), and patient survival.
Main Methods:
- Immunohistochemistry was used to evaluate PD-L1 expression on tumor cells and TILs in 67 MCC specimens.
- Immune infiltrates were characterized phenotypically.
- Associations with MCPyV DNA and overall survival were analyzed.
Main Results:
- PD-L1 expression was observed in 49% of tumor cells and 55% of TILs.
- PD-L1 expression on tumor cells was strongly associated with the presence of TILs and MCPyV.
- MCPyV-negative MCCs uniformly lacked PD-L1 expression.
- PD-L1 negative MCC was independently associated with poorer overall survival (HR 3.12).
Conclusions:
- Tumor cell and TIL PD-L1 expression in MCC is driven by an endogenous, potentially MCPyV-specific immune response.
- PD-L1 expression is a significant prognostic factor in MCC.
- These findings support the investigation of PD-1/PD-L1 blockade therapies for MCC patients.
