Hair(y) Matters in Melanoma Biology

Melanocyte stem cells (MeSCs), one candidate for the cellular origin of melanoma, reside in the bulge region of the hair follicle (HF), an immune-privileged tissue niche with impaired tumor immunosurveillance. Surprisingly, however, primary melanoma is only very rarely associated with HFs. Here, we explore the hypothesis that this profoundly immunoinhibitory signaling environment deprives both MeSCs and melanocytes of the anagen hair matrix of proinflammatory signals required for full oncogenic transformation. Understanding the cellular and molecular mechanisms for generating a putative antimelanoma tissue habitat, namely in the bulge, could help to recreate a similar melanoma-suppressive signaling environment in melanoma high-risk individuals. We further discuss how mimicking the bulge immune privilege may be an effective melanoma prevention strategy.