Highlighted Paper: Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma.

Modi BG, Neustadter J, Binda E, Lewis J, Filler RB, Roberts SJ, Kwong BY, Reddy S, Overton JD, Galan A, Tigelaar R, Cai L, Fu P, Shlomchik M, Kaplan DH, Hayday A, Girardi M. Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science. 2012 Jan 6;335(6064):104-8. (Abstract) (Adrian Hayday).

The paper throws a new light on the myeloid immune cells in the skin, known as Langerhans cells (LC). LC are examples of tissue-resident dendritic cells (DC) that many regard as key to limiting cancer. While LC may do this by activating anti-cancer T cells, the new paper reminds the reader that these cells (as well as their counterparts in other tissues [lung, gut etc]) have a primary role as scavenging “garbage collectors”. This role runs into problems when challenged by industrial hydrocarbons because the cells’ attempts at processing actually promotes the metabolism of the hydrocarbons to more mutagenic forms. Hence, in a widely-used animal model of chemically-induced skin cancer, mutant mice deficient in these cells are completely resistant to developing tumours, unless a downstream mutagenic metabolite is provided. 

Our study then shows that human LC have exactly analogous properties, encouraging people to think more deeply about any treatment regimens that focus on activating such cells.  All the work on human cells, with its major translational impact, was undertaken by Drs Elisa Binda and Adrian Hayday, in the King’s College London Biomedical Research Centre and in the London Research Institute (LRI) of CRUK.