Abstract
Merkel cell polyomavirus (MCPyV) is a common infectious agent that is likely involved in the etiology of most Merkel cell carcinomas (MCC). Serum antibodies recognizing the MCPyV capsid protein VP1 are detectable at high titer in nearly all MCC patients and remain stable over time. Although antibodies to the viral capsid indicate prior MCPyV infection, they provide limited clinical insight into MCC because they are also detected in more than half of the general population. We investigated whether antibodies recognizing MCPyV large and small tumor-associated antigens (T-Ag) would be more specifically associated with MCC. Among 530 population control subjects, these antibodies were present in only 0.9% and were of low titer. In contrast, among 205 MCC cases, 40.5% had serum IgG antibodies that recognize a portion of T-Ag shared between small and large T-Ags. Among cases, titers of T-Ag antibodies fell rapidly (∼8-fold per year) in patients whose cancer did not recur, whereas they rose rapidly in those with progressive disease. Importantly, in several patients who developed metastases, the rise in T-Ag titer preceded clinical detection of disease spread. These results suggest that antibodies recognizing T-Ag are relatively specifically associated with MCC, do not effectively protect against disease progression, and may serve as a clinically useful indicator of disease status.
Highlights
Merkel cell carcinoma (MCC) is an aggressive skin cancer with 35–50% disease-associated mortality [1]
MCC patients are more likely than controls to have antibody responses to Merkel cell polyomavirus (MCPyV) T-Ags
MCC case subjects were more likely to have IgG antibody reactivity to the MCPyV large T and small T-Ag oncoproteins (Table 1)
Summary
Merkel cell carcinoma (MCC) is an aggressive skin cancer with 35–50% disease-associated mortality [1]. The early genes (Tumor-Associated or T antigens, T-Ags) promote cell cycle entry and replication of viral DNA and are expressed from a single transcript. The largest of the T antigen species, aptly named Large T antigen (LT-Ag) is an oncoprotein that is persistently expressed in a truncated form in the majority of MCC tumors and likely promotes cell division in MCC cell lines by inhibition of the tumor suppressor pRb [7,8,9,10]. In contrast to the T antigens, the late genes (viral proteins, or VPs) encode proteins that form the viral capsid, of which VP1 is the major constituent. The capsid is required for initial infection, VP1 expression cannot be detected in MCC tumors [11] and is thought to not play a role in tumor persistence
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