Tumor Infiltrating Immune Cells and Outcome of Merkel Cell Carcinoma: A Population-Based Study

Purpose: Merkel cell carcinoma (MCC) is a rare skin cancer that often harbors Merkel cell polyomavirus (MCPyV) DNA. The clinical importance of intratumoral immune cells and their associations with MCPyV infection are poorly understood. Experimental Design: We identified T lymphocytes (CD3-positive cells), T-cell subsets (CD4, CD8, and FoxP3-positive cells), natural killer cells (small CD16-positive cells), and macrophages (CD68 and CD163-positive cells) in tumors of 116 individuals diagnosed with MCC in Finland from 1979 to 2004 using immunohistochemistry and detected MCPyV DNA with quantitative PCR. The associations between immune cell counts, MCPyV DNA, patient and tumor characteristics, and patient outcome were examined. Results: MCPyV DNA-positive cancers contained higher numbers of CD3(+), CD8(+), CD16(+), FoxP3(+), and CD68(+) cells as compared with MCPyV DNA-negative carcinomas (all P values < 0.05). High intratumoral numbers of CD3(+), CD8(+), or FoxP3(+) cells, and high CD8(+)/CD4(+) or FoxP3(+)/CD4(+) ratios, were significantly associated with favorable overall survival. Individuals with a high tumor CD3(+) count had metastases less often and survived longer, irrespective of the tumor MCPyV status. Tumor CD3(+) count and MCPyV DNA status had independent influence on survival in a Cox multivariable model that also included presence of locoregional metastases at diagnosis and gender as covariates. Conclusions: High intratumoral T-lymphocyte counts are associated with favorable survival in MCC. Although the numbers of T cells are generally higher in MCPyV-positive than in MCPyV-negative MCC, high intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. Clin Cancer Res; 18(10); 2872-81. (C)2012 AACR.