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Merkel polyomavirus provides insights into Merkel cell carcinoma
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NEW YORK — The discovery of the Merkel polyomavirus has led to improved disease tracking and management for patients with Merkel cell carcinoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
Patients’ cellular immune response to the virus also has the potential to information treatment decisions and change survival outcomes in this setting, Paul T. Nghiem, MD, PhD, professor of dermatology/medicine and pathology at the University of Washington Medical School and Seattle Cancer Care Alliance, said during his presentation.
“This cancer is about 30 times less common than melanoma, but three times more likely to kill a patient,” Nghiem. “Its incidence is increasing very rapidly, and there are now around 2,000 cases a year in the U.S.”
The discovery of the cancer-causing Merkel cell polyomavirus in 2008 — which is integrated clonally in eight out of 10 cases of Merkel cell carcinoma — has increased understanding of solid organ tumor immunity, Nghiem said.
“The fascinating thing is that this is a really common virus,” Nghiem said. “It’s on doorknobs, it’s on our skin, it’s in the daycare centers. In 1 in 3,000 people over their lifetime, Merkel cell carcinoma will develop, and it’s typically driven by this virus.”
Understanding the immune response to the virus may help improve the treatment for these patients, Nghiem said. Data indicate that antibodies to T antigen occur in less than 1% of population controls, whereas they occur in nearly 50% of patients newly diagnosed with Merkel cell carcinoma. Further, these antibodies reflect the disease burden.
Nghiem and colleagues used a Merkel polyomavirus serology test to track 219 patients prospectively from the time of diagnosis with their oncoprotein antibodies. The test demonstrated 71% sensitivity and 96% specificity.
“We can use this as a tool to help us do scans a bit less often, and in all seven of the cases in which this antibody showed us the presence of a metastasis, those metastases were clinically occult at the time,” Nghiem said. “This test is much less expensive than a CT, and the sensitivity and specificity are as good or better as CT. It’s not a substitute for CT, but it can tell you when that might be indicated.”
High expression of CD8-positive T cells also is associated with improved survival outcomes among patients with Merkel cell carcinoma. Nghiem and colleagues developed Merkel polyomavirus-specific tetramers — data on which were published in 2011 in Clinical Cancer Research — to identify T cells that would recognize a specific epitope. Results showed 0% of control subjects had T cells that recognized the virus, whereas 64% of patients with Merkel cell carcinoma did.
Afanasiev and colleagues found high T-cell exhaustion based on a dual PD-1 and Tim-3 markers in Merkel-specific T cells in the blood and tumor infiltrating lymphocytes.
Clinical trials are currently recruiting to evaluate PD-1 and PD-L1 targets in Merkel cell carcinoma, Nghiem said.
“Merkel cell polyomavirus provides a unique window into solid tumor immunity in general, and not just in this cancer, but we’re learning tools that we can extend to other cancers,” Nghiem said. “Extensive data demonstrates that CD8 T-cell infiltration is an excellent mark for survival. I believe approximately 30% of these patients will really benefit from immune checkpoint inhibitors. Combined therapies will help in other patients who are not responding.” — by Alexandra Todak
References:
Afanasiev OK, et al. Clin Cancer Res. 2013;doi:10.1158/1078-0432.CCR-13-0035.
Iyer JG, et al. Clin Cancer Res. 2011;doi:10.1158/1078-0432.CCR-11-1513.
Nghiem PT. What’s new in squamous and Merkel cell carcinomas? Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.
Disclosure: Nghiem reports no relevant financial disclosures.