Vaccine and Infectious Disease Division

The hunt for Merkel cell carcinoma-specific T cells

Merkel cell carcinoma (MCC) is an aggressive skin cancer that has a high mortality rate and limited treatment options. Merkel cell polyomavirus (MPCyV) has been recently identified as an essential component for growth of most MCCs. Prevention and control of MCC and other types of cancer is highly associated with patient immune system health. For example, MCC occurs much more frequently in transplant patients or HIV-infected persons with damaged immune systems. T cells are a component of the immune system that can recognize and target specific viral proteins, and have also been shown to be critical in regulating and preventing many types of cancer. It is currently unknown if T cells target specific MPCyV proteins, what these viral proteins might be, and if these T cells can traffic to MCC tumor masses.

VIDD affiliate investigator Dr. David Koelle co-directed a study investigating this question using tumor biopsies from MCC tumors. The authors analyzed human T-cell responses to MPCyV proteins from the biopsies to determine if MPCyV-responsive T cells can be recovered from MCC tumors, and if so, what viral proteins are responsible for this T-cell response. T cells from MCC patient biopsies were purified and subsequently tested for virus-specific T-cell activation, in collaboration with SCCA colleagues. The authors identified CD8 and CD4 T cells that were specifically activated by several MPCyV viral proteins, and found that a subset of these T cells was highly enriched in the tumor when compared to patient blood, suggesting that these cells are preferentially recruited to the MCC tumor site. This is the first study to analyze T-cell responses to MCPyV and to demonstrate that T cells can recognize and target specific MPCyV protein sequences in MCC tumors.

Iyer JG, Afanasiev OK, McClurkan C, Paulson KG, Nagase K, Jing L, Marshak JO, Dong L, Carter JJ, Lai I, Farrar EA, Byrd D, Galloway DA, Yee C, Koelle DM, Nghiem P.  Merkel cell polyomavirus-specific CD8+ and CD4+ T-cell responses identified in Merkel cell carcinomas and blood.  Clin Cancer Res. 2011 Sep 9. [Epub ahead of print]