Editors' ChoiceImmunotherapy

A Cancer Drug Promotes Hair Growth

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Science Translational Medicine  24 Sep 2014:
Vol. 6, Issue 255, pp. 255ec164
DOI: 10.1126/scitranslmed.3010412

When a patient diagnosed with cancer begins treatment, a common question is, “Will this medication make me lose my hair?” Hair loss is often associated with cancer chemotherapy, and although it can cause emotional distress, it is typically transient. Some forms of hair loss, such as alopecia areata, are mediated not by drugs but by an autoimmune process. Until now, the mechanism of autoimmunity in this disease was undefined, although genome-wide association studies suggested a role for the NKG2D ligands ULBP3 and MICA. NKG2D is an activating receptor found on cytotoxic T cells and Natural Killer (NK) cells.

Xing and colleagues demonstrate that NKG2D+CD8+ T cells are necessary and sufficient to cause alopecia areata in a mouse model prone to the disease. These T cells infiltrate the skin in affected mice, draining lymph nodes, and display a transcriptional profile of activated cytotoxic T lymphocytes (CTLs) with up-regulation of interferon-response genes and common-gamma chain cytokines and their receptors (type I cytokines). Because many of these cytokines signal via Janus kinases (JAKs) , the authors hypothesized that the JAK1 and JAK2 inhibitor ruxolitinib or the JAK3 inhibitor tofacitinib could have therapeutic effects. Encouragingly, both ruxolinitib and tofacitinib, administered orally or topically, were able to prevent disease and restore hair growth in mice. The drugs also blocked the inflammatory gene expression signatures in skin.

Ruxolinitib is currently approved for the blood cancer myelofibrosis and is often used in other JAK2 mutation-driven malignancies; tofacitinib is approved for rheumatoid arthritis. Xing et al. treated three patients with alopecia areata with oral ruxolinitib, and all three had nearly complete restoration of hair growth within months. These data bridge what has been learned from aberrant signal transduction pathways in cancer with pathways of cellular immune responses to open new avenues for treating autoimmune disease.

L. Xing et al., Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat. Med. 20, 1043–1049 (2014). [Full Text]

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