Abnormal Numbers of Certain T-Cells May Explain Melanoma-Sarcoidosis Link

Increased levels of a specific type of T-cell in some patients with melanoma might explain the connection between the cancer and sarcoidosis, researchers suggest in a study that explored melanoma patients treated with immunotherapy.

The study, “Immunotherapy-induced sarcoidosis in patients with melanoma treated with PD-1 checkpoint inhibitors: Case series and immunophenotypic analysis,” was published in the International Journal of Rheumatic Diseases.

Sarcoidosis has been linked to a diagnosis of melanoma, but researchers also believe that the inflammatory disease can be triggered by melanoma treatment.

In an attempt to study factors behind these associations, researchers at the cancer center Chris O’Brien Lifehouse and the University of Sydney — both in Australia — took a closer look at melanoma patients enrolled in clinical trials testing cancer immunotherapies.

The team did, however, analyze the presence of specific immune cells before the start of treatment, comparing data from those with sarcoidosis to melanoma patients who did not develop the granulomatous inflammatory disease.

Two patients in the studies who developed sarcoidosis after immunotherapy had stored blood samples from before the start of treatment. One had been treated with Keytruda (pembrolizumab; Merck) for two weeks when she started developing unspecific symptoms such as fever, dry cough, fatigue, nausea, and vomiting.

She later developed swollen nodules on her arms and legs, and after extensive tests, doctors diagnosed her with sarcoidosis. When she paused treatment with Keytruda, her symptoms gradually became better. They did not return when she resumed therapy with Keytruda.

The second patient developed symptoms in the form of subcutaneous lesions after two months of treatment with Opdivo (nivolumab; Bristol-Myers Squibb). Lung scans revealed enlarged lymph nodes, and doctors first thought the patient’s cancer had spread. Tissue analysis, however, indicated sarcoidosis. The patient was switched to another cancer drug, called Yervoy (ipilimumab; Bristol-Myers Squibb).

Since the patient also developed an inflammatory gut condition, he was treated with high-dose corticosteroids and a TNF-blocking drug, which eventually stabilized his sarcoidosis.

Immune cell analysis revealed that the two patients, along with three out of 13 who had not developed sarcoidosis, had increased levels of a cell type known as Th17.1. Other investigated T-cell types were found in similar numbers in patients with and without sarcoidosis.

This, the researchers argued, might indicate that the Th17.1 cell type is a driver of sarcoidosis in melanoma patients. Cancer immunotherapy might then further enhance the abnormality. The team, however, did not analyze how the cell numbers had changed with the treatment.