Lenalidomide increases peripheral T regulatory phenotype cells in patients with HIV associated Kaposi Sarcoma (P2030)

Kaposi Sarcoma, an angioproliferative vascular tumor, is the most common malignancy in patients with HIV and presents a treatment conundrum because of its variable natural history. Lenalidomide is a drug that has immune-modulatory, anti-neoplastic, and anti-angiogenic properties. It is used in the treatment of myelodysplastic disease and multiple myeloma, but its in vivo effects on peripheral blood immune activity is not fully explored. In this preliminary report from a phase I/II trial of lenalidomide in the treatment of HIV associated Kaposi Sarcoma, we found that lenalidomide increased the number and percentage of T regulatory phenotype cells in the peripheral blood. In patients with measurable regression of Kaposi Sarcoma lesion size as well as number of lesions, there was also an observable accumulation in FOXP3 expressing cells in the Kaposi Sarcoma lesion. These findings enable us to speculate on three novel concepts: 1) lenalidomide increases the frequency of circulating T regulatory phenotype cells, 2) lenalidomide’s anti-angiogenic mechanism may be due to T regulatory cell induction, and 3) in contrast to their role in promoting tumor growth by inhibiting tumor immunosurveillance, T regulatory cells may inhibit angioproliferative tumors therefore act as an effective therapeutic agent for tumors such as Kaposi Sarcoma.