Overexpression of hypoxia‐inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides—Cutaneous T‐cell lymphoma: Clinical implications

Abstract

Mycosis fungoides (MF) is the most common variant of primary cutaneous T‐cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia‐inducible factor 1 alpha (HIF‐1α) may regulate FoxP3 expression; however, it is unknown whether HIF‐1α is expressed in the CD4⁺ T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF‐1α and FoxP3 in CD4⁺ T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4⁺ T cells with an aberrant phenotype among early stage MF patients. HIF‐1α was overexpressed in these CD4⁺ T cells. In addition, we found a decrease in the percentage of FoxP3⁺ cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF‐1α and FoxP3 expression. Skin HIF‐1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF‐1α degradation increases the percentage of FoxP3⁺ T cells in skin lesions. Our results suggest that overexpression of HIF‐1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.