PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival

Evan J. Lipson, Jeremy G. Vincent, Myriam Loyo, Luciane T. Kagohara, Brandon S. Luber, Hao Wang, Haiying Xu, Suresh K. Nayar, Timothy S. Wang, David Sidransky, Robert A. Anders, Suzanne L. Topalian, Janis M. Taube

Research output: Contribution to journalArticle

220 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)54-63
Number of pages10
JournalCancer Immunology Research
Volume1
Issue number1
DOIs
StatePublished - Jul 1 2013

Keywords

  • B7-H1
  • Merkel cell carcinoma
  • Merkel cell polyomavirus
  • PD-L1
  • immunotherapy

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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  • Cite this

    Lipson, E. J., Vincent, J. G., Loyo, M., Kagohara, L. T., Luber, B. S., Wang, H., Xu, H., Nayar, S. K., Wang, T. S., Sidransky, D., Anders, R. A., Topalian, S. L., & Taube, J. M. (2013). PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunology Research, 1(1), 54-63. https://doi.org/10.1158/2326-6066.CIR-13-0034